7-50628397-C-T

Variant names:

• chr7-50628397-C-T
• rs980716
• NM_001350814.2:c.505-1419G>A

Variant summary

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

The NM_001350814.2(GRB10):​c.505-1419G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 152,028 control chromosomes in the GnomAD database, including 48,097 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 0.79 (48097 hom., cov: 31)
• Consequence: GRB10 NM_001350814.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.902
• Publications: 7 publications found

Genes affected

GRB10 (HGNC:4564): (growth factor receptor bound protein 10) The product of this gene belongs to a small family of adapter proteins that are known to interact with a number of receptor tyrosine kinases and signaling molecules. This gene encodes a growth factor receptor-binding protein that interacts with insulin receptors and insulin-like growth-factor receptors. Overexpression of some isoforms of the encoded protein inhibits tyrosine kinase activity and results in growth suppression. This gene is imprinted in a highly isoform- and tissue-specific manner, with expression observed from the paternal allele in the brain, and from the maternal allele in the placental trophoblasts. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2010]

ENSG00000286658 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRB10	NM_001350814.2	c.505-1419G>A		intron_variant	Intron 7 of 18	ENST00000401949.6	NP_001337743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRB10	ENST00000401949.6	c.505-1419G>A		intron_variant	Intron 7 of 18	1	NM_001350814.2	ENSP00000385770.1

Frequencies

GnomAD3 genomes AF: 0.794 AC: 120621 AN: 151910 Hom.: 48062 Cov.: 31

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.891

Gnomad AMR AF: 0.865

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.780

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.811

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

GnomAD4 genome AF: 0.794 AC: 120710 AN: 152028 Hom.: 48097 Cov.: 31 AF XY: 0.792 AC XY: 58818 AN XY: 74304

African (AFR) AF: 0.790 AC: 32739 AN: 41436

American (AMR) AF: 0.865 AC: 13236 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2598 AN: 3470

East Asian (EAS) AF: 0.932 AC: 4809 AN: 5162

South Asian (SAS) AF: 0.667 AC: 3213 AN: 4816

European-Finnish (FIN) AF: 0.750 AC: 7920 AN: 10554

Middle Eastern (MID) AF: 0.784 AC: 229 AN: 292

European-Non Finnish (NFE) AF: 0.786 AC: 53439 AN: 67976

Other (OTH) AF: 0.811 AC: 1714 AN: 2114

Alfa AF: 0.792 Hom.: 73984

Bravo AF: 0.810

Asia WGS AF: 0.816 AC: 2836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.16
DANN	Benign	0.40
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs980716; hg19: chr7-50696094;