rs2288657

Variant names:

• chr2-127637923-C-T
• rs2288657
• NM_001393586.1:c.*506C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001393586.1(MYO7B):​c.*506C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0585 in 152,264 control chromosomes in the GnomAD database, including 327 homozygotes. 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: 𝑓 0.059 (327 hom., cov: 33)
• Consequence: MYO7B NM_001393586.1 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135
• Publications: 15 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO7B	NM_001393586.1	c.*506C>T		downstream_gene_variant		ENST00000409816.8	NP_001380515.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO7B	ENST00000409816.8	c.*506C>T		downstream_gene_variant		1	NM_001393586.1	ENSP00000386461.3

Frequencies

GnomAD3 genomes AF: 0.0583 AC: 8877 AN: 152146 Hom.: 319 Cov.: 33

Gnomad AFR AF: 0.0913

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0409

Gnomad ASJ AF: 0.0484

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.00960

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0409

Gnomad OTH AF: 0.0612

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0585 AC: 8912 AN: 152264 Hom.: 327 Cov.: 33 AF XY: 0.0588 AC XY: 4375 AN XY: 74448

African (AFR) AF: 0.0917 AC: 3810 AN: 41550

American (AMR) AF: 0.0408 AC: 625 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0484 AC: 168 AN: 3470

East Asian (EAS) AF: 0.140 AC: 723 AN: 5160

South Asian (SAS) AF: 0.105 AC: 504 AN: 4818

European-Finnish (FIN) AF: 0.00960 AC: 102 AN: 10622

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0409 AC: 2784 AN: 68024

Other (OTH) AF: 0.0643 AC: 136 AN: 2114

Alfa AF: 0.0475 Hom.: 311

Bravo AF: 0.0624

Asia WGS AF: 0.122 AC: 425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	8.1
DANN	Benign	0.62
PhyloP100		-0.14

Splicing

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

Other links and lift over

dbSNP: rs2288657; hg19: chr2-128395498;