7-50674483-C-T

Variant names:

• chr7-50674483-C-T
• rs1800504
• NM_001350814.2:c.315G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001350814.2(GRB10):​c.315G>A​(p.Pro105Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 1,608,166 control chromosomes in the GnomAD database, including 235,632 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 0.56 (24571 hom., cov: 34)
  • Exomes 𝑓: 0.54 (211061 hom.)
• Consequence: GRB10 NM_001350814.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.40
• Publications: 33 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=-3.4 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.651 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.315G>A	p.Pro105Pro	synonymous	Exon 6 of 19	NP_001337743.1	Q13322-1
	GRB10	NM_001371009.1		c.462G>A	p.Pro154Pro	synonymous	Exon 3 of 16	NP_001357938.1
	GRB10	NM_001350815.2		c.429G>A	p.Pro143Pro	synonymous	Exon 3 of 16	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.315G>A	p.Pro105Pro	synonymous	Exon 6 of 19	ENSP00000385770.1	Q13322-1
	GRB10	ENST00000398812.6	TSL:1	c.315G>A	p.Pro105Pro	synonymous	Exon 3 of 16	ENSP00000381793.2	Q13322-1
	GRB10	ENST00000357271.9	TSL:1	c.315G>A	p.Pro105Pro	synonymous	Exon 3 of 15	ENSP00000349818.5	Q13322-2

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85492 AN: 152076 Hom.: 24547 Cov.: 34

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.582

GnomAD2 exomes AF: 0.517 AC: 126579 AN: 244630 AF XY: 0.513

Gnomad AFR exome AF: 0.666

Gnomad AMR exome AF: 0.501

Gnomad ASJ exome AF: 0.527

Gnomad EAS exome AF: 0.420

Gnomad FIN exome AF: 0.407

Gnomad NFE exome AF: 0.548

Gnomad OTH exome AF: 0.538

GnomAD4 exome AF: 0.535 AC: 779672 AN: 1455970 Hom.: 211061 Cov.: 72 AF XY: 0.533 AC XY: 385942 AN XY: 724574

African (AFR) AF: 0.651 AC: 21792 AN: 33462

American (AMR) AF: 0.507 AC: 22682 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 13730 AN: 26136

East Asian (EAS) AF: 0.363 AC: 14411 AN: 39696

South Asian (SAS) AF: 0.461 AC: 39743 AN: 86234

European-Finnish (FIN) AF: 0.414 AC: 19934 AN: 48118

Middle Eastern (MID) AF: 0.490 AC: 2630 AN: 5364

European-Non Finnish (NFE) AF: 0.551 AC: 612393 AN: 1111930

Other (OTH) AF: 0.536 AC: 32357 AN: 60316

GnomAD4 genome AF: 0.562 AC: 85560 AN: 152196 Hom.: 24571 Cov.: 34 AF XY: 0.552 AC XY: 41038 AN XY: 74408

African (AFR) AF: 0.657 AC: 27286 AN: 41524

American (AMR) AF: 0.584 AC: 8941 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1790 AN: 3468

East Asian (EAS) AF: 0.397 AC: 2048 AN: 5164

South Asian (SAS) AF: 0.461 AC: 2227 AN: 4830

European-Finnish (FIN) AF: 0.399 AC: 4226 AN: 10588

Middle Eastern (MID) AF: 0.545 AC: 159 AN: 292

European-Non Finnish (NFE) AF: 0.546 AC: 37132 AN: 68010

Other (OTH) AF: 0.582 AC: 1229 AN: 2112

Alfa AF: 0.556 Hom.: 50869

Bravo AF: 0.576

Asia WGS AF: 0.518 AC: 1802 AN: 3478

EpiCase AF: 0.544

EpiControl AF: 0.549

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	4.2
DANN	Benign	0.55
PhyloP100		-3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
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: rs1800504; hg19: chr7-50742180; COSMIC: COSV60007255; COSMIC: COSV60007255;