chr7-50701554-G-A

Variant names:

• chr7-50701554-G-A
• rs4521715
• NM_001350814.2:c.139+2267C>T

Variant summary

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

The NM_001350814.2(GRB10):​c.139+2267C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 152,076 control chromosomes in the GnomAD database, including 31,722 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 0.62 (31722 hom., cov: 32)
• Consequence: GRB10 NM_001350814.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.680
• Publications: 5 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350814.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRB10	NM_001350814.2	MANE Select	c.139+2267C>T		intron	N/A	NP_001337743.1	Q13322-1
	GRB10	NM_001371009.1		c.287-26896C>T		intron	N/A	NP_001357938.1
	GRB10	NM_001350815.2		c.254-26896C>T		intron	N/A	NP_001337744.1	A0A2R8YCL1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRB10	ENST00000401949.6	TSL:1 MANE Select	c.139+2267C>T		intron	N/A	ENSP00000385770.1	Q13322-1
	GRB10	ENST00000398812.6	TSL:1	c.139+2267C>T		intron	N/A	ENSP00000381793.2	Q13322-1
	GRB10	ENST00000357271.9	TSL:1	c.139+2267C>T		intron	N/A	ENSP00000349818.5	Q13322-2

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93797 AN: 151958 Hom.: 31727 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.749

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.617 AC: 93814 AN: 152076 Hom.: 31722 Cov.: 32 AF XY: 0.612 AC XY: 45508 AN XY: 74322

African (AFR) AF: 0.323 AC: 13373 AN: 41456

American (AMR) AF: 0.715 AC: 10931 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.839 AC: 2913 AN: 3472

East Asian (EAS) AF: 0.737 AC: 3816 AN: 5176

South Asian (SAS) AF: 0.693 AC: 3339 AN: 4818

European-Finnish (FIN) AF: 0.577 AC: 6099 AN: 10566

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.749 AC: 50933 AN: 67976

Other (OTH) AF: 0.688 AC: 1453 AN: 2112

Alfa AF: 0.659 Hom.: 4549

Bravo AF: 0.609

Asia WGS AF: 0.727 AC: 2530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.95
DANN	Benign	0.43
PhyloP100		-0.68
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: rs4521715; hg19: chr7-50769251;