Genetic Variant MYO7B:c.132+8T>C (chr2-127564274-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001393586.1(MYO7B):c.132+8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000907 in 1,553,878 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0048 ( 7 hom., cov: 33)

Exomes 𝑓: 0.00048 ( 5 hom. )

Consequence

MYO7B
NM_001393586.1 splice_region, intron

Scores

Splicing: ADA: 0.0005890

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.545

Publications

0 publications found

Variant links:

Genes affected

MYO7B (HGNC:7607): (myosin VIIB) The protein encoded by this gene is found in brush border microvilli of epithelial cells in the intestines and kidneys. The encoded protein is involved in linking protocadherins to the actin cytoskeleton and is essential for proper microvilli function. This protein aids in the accumulation of intermicrovillar adhesion components such as harmonin and ANKS4B, and this accumulation is necessary for normal brush border action. [provided by RefSeq, Jan 2017]

MYO7B links:

LOC105373609 (HGNC:):

LOC105373609 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 2-127564274-T-C is Benign according to our data. Variant chr2-127564274-T-C is described in ClinVar as Benign. ClinVar VariationId is 3035564.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00481 (733/152244) while in subpopulation AFR AF = 0.0169 (701/41548). AF 95% confidence interval is 0.0158. There are 7 homozygotes in GnomAd4. There are 347 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393586.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYO7B	NM_001393586.1	MANE Select	c.132+8T>C	splice_region intron	N/A	NP_001380515.1	A0A8C8KL71
MYO7B	NM_001080527.2		c.132+8T>C	splice_region intron	N/A	NP_001073996.1	Q6PIF6-1
LOC105373609	NR_132317.1		n.182+414A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYO7B	ENST00000409816.8	TSL:1 MANE Select	c.132+8T>C	splice_region intron	N/A	ENSP00000386461.3	A0A8C8KL71
MYO7B	ENST00000897059.1		c.132+8T>C	splice_region intron	N/A	ENSP00000567118.1
MYO7B	ENST00000428314.5	TSL:5	c.132+8T>C	splice_region intron	N/A	ENSP00000415090.1	Q6PIF6-1

Frequencies

GnomAD3 genomes

AF:

0.00479

AC:

728

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0168

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00383

GnomAD2 exomes

AF:

0.00103

AC:

171

AN:

165734

AF XY:

0.000765

show subpopulations

Gnomad AFR exome

AF:

0.0154

Gnomad AMR exome

AF:

0.00109

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000445

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000483

AC:

677

AN:

1401634

Hom.:

Cov.:

AF XY:

0.000435

AC XY:

301

AN XY:

692398

show subpopulations

African (AFR)

AF:

0.0167

AC:

533

AN:

32008

American (AMR)

AF:

0.000940

AC:

AN:

36160

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25152

East Asian (EAS)

AF:

0.00

AC:

AN:

36232

South Asian (SAS)

AF:

0.0000881

AC:

AN:

79426

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49928

Middle Eastern (MID)

AF:

0.00176

AC:

AN:

5692

European-Non Finnish (NFE)

AF:

0.00000927

AC:

AN:

1078742

Other (OTH)

AF:

0.00142

AC:

AN:

58294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

105

140

175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00481

AC:

733

AN:

152244

Hom.:

Cov.:

AF XY:

0.00466

AC XY:

347

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0169

AC:

701

AN:

41548

American (AMR)

AF:

0.00157

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67998

Other (OTH)

AF:

0.00379

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

116

155

194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00229

Hom.:

Bravo

AF:

0.00549

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

MYO7B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

3.1

(source)

DANN

Benign

0.63

PhyloP100

-0.55

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00059

dbscSNV1_RF

Benign

0.0040

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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