7-50605332-T-C

Variant names:

• chr7-50605332-T-C
• rs4947710
• NM_001350814.2:c.1347A>G

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.1347A>G​(p.Ala449Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 1,613,938 control chromosomes in the GnomAD database, including 640,106 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 0.87 (57943 hom., cov: 33)
  • Exomes 𝑓: 0.89 (582163 hom.)
• Consequence: GRB10 NM_001350814.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -7.17
• Publications: 29 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=-0.94).
• BP7: Synonymous conserved (PhyloP=-7.16 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 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.1347A>G	p.Ala449Ala	synonymous	Exon 15 of 19	NP_001337743.1	Q13322-1
	GRB10	NM_001371009.1		c.1494A>G	p.Ala498Ala	synonymous	Exon 12 of 16	NP_001357938.1
	GRB10	NM_001350815.2		c.1461A>G	p.Ala487Ala	synonymous	Exon 12 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.1347A>G	p.Ala449Ala	synonymous	Exon 15 of 19	ENSP00000385770.1	Q13322-1
	GRB10	ENST00000398812.6	TSL:1	c.1347A>G	p.Ala449Ala	synonymous	Exon 12 of 16	ENSP00000381793.2	Q13322-1
	GRB10	ENST00000357271.9	TSL:1	c.1209A>G	p.Ala403Ala	synonymous	Exon 11 of 15	ENSP00000349818.5	Q13322-2

Frequencies

GnomAD3 genomes AF: 0.871 AC: 132540 AN: 152158 Hom.: 57909 Cov.: 33

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.954

Gnomad AMR AF: 0.892

Gnomad ASJ AF: 0.951

Gnomad EAS AF: 0.926

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.902

Gnomad OTH AF: 0.894

GnomAD2 exomes AF: 0.880 AC: 219578 AN: 249386 AF XY: 0.882

Gnomad AFR exome AF: 0.821

Gnomad AMR exome AF: 0.874

Gnomad ASJ exome AF: 0.954

Gnomad EAS exome AF: 0.922

Gnomad FIN exome AF: 0.755

Gnomad NFE exome AF: 0.903

Gnomad OTH exome AF: 0.897

GnomAD4 exome AF: 0.892 AC: 1303382 AN: 1461662 Hom.: 582163 Cov.: 57 AF XY: 0.892 AC XY: 648337 AN XY: 727148

African (AFR) AF: 0.821 AC: 27478 AN: 33478

American (AMR) AF: 0.874 AC: 39087 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.955 AC: 24956 AN: 26134

East Asian (EAS) AF: 0.925 AC: 36710 AN: 39700

South Asian (SAS) AF: 0.867 AC: 74766 AN: 86252

European-Finnish (FIN) AF: 0.767 AC: 40913 AN: 53324

Middle Eastern (MID) AF: 0.915 AC: 5277 AN: 5768

European-Non Finnish (NFE) AF: 0.900 AC: 1000210 AN: 1111898

Other (OTH) AF: 0.894 AC: 53985 AN: 60388

GnomAD4 genome AF: 0.871 AC: 132621 AN: 152276 Hom.: 57943 Cov.: 33 AF XY: 0.864 AC XY: 64330 AN XY: 74452

African (AFR) AF: 0.826 AC: 34351 AN: 41568

American (AMR) AF: 0.891 AC: 13639 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.951 AC: 3302 AN: 3472

East Asian (EAS) AF: 0.926 AC: 4779 AN: 5162

South Asian (SAS) AF: 0.864 AC: 4161 AN: 4816

European-Finnish (FIN) AF: 0.752 AC: 7977 AN: 10608

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.902 AC: 61372 AN: 68024

Other (OTH) AF: 0.896 AC: 1895 AN: 2116

Alfa AF: 0.896 Hom.: 179280

Bravo AF: 0.878

Asia WGS AF: 0.911 AC: 3170 AN: 3478

EpiCase AF: 0.912

EpiControl AF: 0.913

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.044
DANN	Benign	0.26
PhyloP100		-7.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4947710; hg19: chr7-50673029; COSMIC: COSV60010970;