rs2668898

Variant names:

• chr11-61958026-A-G
• rs2668898
• NM_004183.4:c.715-120A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-61958026-A-G
• chr11-61958026-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004183.4(BEST1):​c.715-120A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 1,520,098 control chromosomes in the GnomAD database, including 98,908 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (13423 hom., cov: 32)
  • Exomes 𝑓: 0.32 (85485 hom.)
• Consequence: BEST1 NM_004183.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.22
• Publications: 10 publications found

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, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P
• inherited retinal dystrophy

  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, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
• autosomal recessive bestrophinopathy

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• retinitis pigmentosa 50

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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

LOC107984334 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 11-61958026-A-G is Benign according to our data. Variant chr11-61958026-A-G is described in ClinVar as Benign. ClinVar VariationId is 1281169.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BEST1	NM_004183.4	c.715-120A>G		intron_variant	Intron 6 of 10	ENST00000378043.9	NP_004174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BEST1	ENST00000378043.9	c.715-120A>G		intron_variant	Intron 6 of 10	1	NM_004183.4	ENSP00000367282.4

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58924 AN: 151836 Hom.: 13416 Cov.: 32

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.326

GnomAD4 exome AF: 0.319 AC: 436446 AN: 1368144 Hom.: 85485 AF XY: 0.327 AC XY: 223859 AN XY: 684508

African (AFR) AF: 0.540 AC: 17148 AN: 31766

American (AMR) AF: 0.422 AC: 18427 AN: 43634

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 4747 AN: 25258

East Asian (EAS) AF: 0.913 AC: 35767 AN: 39192

South Asian (SAS) AF: 0.643 AC: 53715 AN: 83590

European-Finnish (FIN) AF: 0.400 AC: 16954 AN: 42370

Middle Eastern (MID) AF: 0.239 AC: 1014 AN: 4244

European-Non Finnish (NFE) AF: 0.259 AC: 269250 AN: 1040650

Other (OTH) AF: 0.338 AC: 19424 AN: 57440

GnomAD4 genome AF: 0.388 AC: 58973 AN: 151954 Hom.: 13423 Cov.: 32 AF XY: 0.402 AC XY: 29845 AN XY: 74244

African (AFR) AF: 0.529 AC: 21924 AN: 41430

American (AMR) AF: 0.354 AC: 5406 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 676 AN: 3466

East Asian (EAS) AF: 0.878 AC: 4524 AN: 5152

South Asian (SAS) AF: 0.668 AC: 3220 AN: 4820

European-Finnish (FIN) AF: 0.418 AC: 4402 AN: 10542

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17926 AN: 67956

Other (OTH) AF: 0.323 AC: 683 AN: 2114

Alfa AF: 0.287 Hom.: 1280

Bravo AF: 0.390

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.61
DANN	Benign	0.49
PhyloP100		-5.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2668898; hg19: chr11-61725498;