2-127631287-G-A

Variant names:

• chr2-127631287-G-A
• rs13025959
• NM_001393586.1:c.5019G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The ENST00000409816.8(MYO7B):​c.5019G>A​(p.Glu1673Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MYO7B ENST00000409816.8 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.24
• Publications: 26 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=2.24 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000409816.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO7B	NM_001393586.1	MANE Select	c.5019G>A	p.Glu1673Glu	synonymous	Exon 37 of 48	NP_001380515.1
	MYO7B	NM_001080527.2		c.4941G>A	p.Glu1647Glu	synonymous	Exon 36 of 47	NP_001073996.1
	MYO7B	NM_001393594.1		c.1500G>A	p.Glu500Glu	synonymous	Exon 12 of 23	NP_001380523.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO7B	ENST00000409816.8	TSL:1 MANE Select	c.5019G>A	p.Glu1673Glu	synonymous	Exon 37 of 48	ENSP00000386461.3
	MYO7B	ENST00000409090.1	TSL:1	c.1500G>A	p.Glu500Glu	synonymous	Exon 12 of 23	ENSP00000386850.1
	MYO7B	ENST00000496841.5	TSL:1	n.1963G>A		non_coding_transcript_exon	Exon 11 of 19

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459582 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 725980

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.0000224 AC: 1 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.00 AC: 0 AN: 86186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111260

Other (OTH) AF: 0.00 AC: 0 AN: 60306

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 765

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.3
DANN	Benign	0.33
PhyloP100		2.2
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs13025959; hg19: chr2-128388862;