NM_004183.4:c.715-12_715-4dupTCCTCCTCC

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_004183.4(BEST1):c.715-12_715-4dupTCCTCCTCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 1,544,446 control chromosomes in the GnomAD database, including 560,870 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.92 ( 64168 hom., cov: 0)

Exomes 𝑓: 0.85 ( 496702 hom. )

Consequence

BEST1
NM_004183.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -3.82

Publications

0 publications found

Variant links:

Genes affected

BEST1 (HGNC:12703): (bestrophin 1) This gene encodes a member of the bestrophin gene family. This small gene family is characterized by proteins with a highly conserved N-terminus with four to six transmembrane domains. Bestrophins may form chloride ion channels or may regulate voltage-gated L-type calcium-ion channels. Bestrophins are generally believed to form calcium-activated chloride-ion channels in epithelial cells but they have also been shown to be highly permeable to bicarbonate ion transport in retinal tissue. Mutations in this gene are responsible for juvenile-onset vitelliform macular dystrophy (VMD2), also known as Best macular dystrophy, in addition to adult-onset vitelliform macular dystrophy (AVMD) and other retinopathies. Alternative splicing results in multiple variants encoding distinct isoforms.[provided by RefSeq, Nov 2008]

BEST1 Gene-Disease associations (from GenCC):

autosomal dominant vitreoretinochoroidopathy
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, G2P, Labcorp Genetics (formerly Invitae)
BEST1-related dominant retinopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
retinitis pigmentosa
Inheritance: AD, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
vitelliform macular dystrophy 2
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
autosomal recessive bestrophinopathy
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
retinitis pigmentosa 50
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
adult-onset foveomacular vitelliform dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
MRCS syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
nanophthalmia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

BEST1 links:

LOC107984334 (HGNC:):

LOC107984334 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 11-61958127-A-ATCCTCCTCC is Benign according to our data. Variant chr11-61958127-A-ATCCTCCTCC is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 166753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004183.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BEST1	NM_004183.4	MANE Select	c.715-12_715-4dupTCCTCCTCC	splice_region intron	N/A	NP_004174.1	O76090-1
BEST1	NM_001440571.1		c.715-12_715-4dupTCCTCCTCC	splice_region intron	N/A	NP_001427500.1
BEST1	NM_001440572.1		c.715-12_715-4dupTCCTCCTCC	splice_region intron	N/A	NP_001427501.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BEST1	ENST00000378043.9	TSL:1 MANE Select	c.715-19_715-18insTCCTCCTCC	intron	N/A	ENSP00000367282.4	O76090-1
BEST1	ENST00000449131.6	TSL:1	c.535-19_535-18insTCCTCCTCC	intron	N/A	ENSP00000399709.2	O76090-3
BEST1	ENST00000526988.1	TSL:2	c.397-19_397-18insTCCTCCTCC	intron	N/A	ENSP00000433195.1	B7Z1N8

Frequencies

GnomAD3 genomes

AF:

0.921

AC:

139222

AN:

151124

Hom.:

64132

Cov.:

show subpopulations

Gnomad AFR

AF:

0.922

Gnomad AMI

AF:

0.902

Gnomad AMR

AF:

0.907

Gnomad ASJ

AF:

0.941

Gnomad EAS

AF:

0.997

Gnomad SAS

AF:

0.967

Gnomad FIN

AF:

0.905

Gnomad MID

AF:

0.939

Gnomad NFE

AF:

0.917

Gnomad OTH

AF:

0.924

GnomAD4 exome

AF:

0.853

AC:

1188402

AN:

1393208

Hom.:

496702

Cov.:

AF XY:

0.854

AC XY:

592245

AN XY:

693658

show subpopulations

African (AFR)

AF:

0.853

AC:

27223

AN:

31928

American (AMR)

AF:

0.841

AC:

36172

AN:

43000

Ashkenazi Jewish (ASJ)

AF:

0.858

AC:

21220

AN:

24734

East Asian (EAS)

AF:

0.911

AC:

33967

AN:

37270

South Asian (SAS)

AF:

0.879

AC:

72557

AN:

82536

European-Finnish (FIN)

AF:

0.836

AC:

42302

AN:

50616

Middle Eastern (MID)

AF:

0.893

AC:

4942

AN:

5534

European-Non Finnish (NFE)

AF:

0.850

AC:

900936

AN:

1060062

Other (OTH)

AF:

0.853

AC:

49083

AN:

57528

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.655

Heterozygous variant carriers

11589

23178

34768

46357

57946

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20526

41052

61578

82104

102630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.921

AC:

139313

AN:

151238

Hom.:

64168

Cov.:

AF XY:

0.921

AC XY:

68090

AN XY:

73892

show subpopulations

African (AFR)

AF:

0.922

AC:

38031

AN:

41258

American (AMR)

AF:

0.907

AC:

13783

AN:

15196

Ashkenazi Jewish (ASJ)

AF:

0.941

AC:

3240

AN:

3444

East Asian (EAS)

AF:

0.997

AC:

5125

AN:

5138

South Asian (SAS)

AF:

0.966

AC:

4603

AN:

4764

European-Finnish (FIN)

AF:

0.905

AC:

9488

AN:

10482

Middle Eastern (MID)

AF:

0.935

AC:

273

AN:

292

European-Non Finnish (NFE)

AF:

0.917

AC:

62026

AN:

67668

Other (OTH)

AF:

0.922

AC:

1925

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

523

1046

1569

2092

2615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

900

1800

2700

3600

4500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.826

Hom.:

4495

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-3.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over