7-50617905-T-G

Position:

• chr7-50617905-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001350814.2(GRB10):​c.846+166A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 671,818 control chromosomes in the GnomAD database, including 8,434 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 0.13 (1566 hom., cov: 33)
  • Exomes 𝑓: 0.15 (6868 hom.)
• Consequence: GRB10 NM_001350814.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.176

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRB10	NM_001350814.2	c.846+166A>C		intron_variant		ENST00000401949.6	NP_001337743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRB10	ENST00000401949.6	c.846+166A>C		intron_variant		1	NM_001350814.2	ENSP00000385770.1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19854 AN: 152160 Hom.: 1568 Cov.: 33

Gnomad AFR AF: 0.0592

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0165

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.130

GnomAD4 exome AF: 0.153 AC: 79260 AN: 519540 Hom.: 6868 Cov.: 5 AF XY: 0.151 AC XY: 42326 AN XY: 279700

Gnomad4 AFR exome AF: 0.0594

Gnomad4 AMR exome AF: 0.0981

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.0278

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.214

Gnomad4 NFE exome AF: 0.175

Gnomad4 OTH exome AF: 0.140

GnomAD4 genome AF: 0.130 AC: 19857 AN: 152278 Hom.: 1566 Cov.: 33 AF XY: 0.131 AC XY: 9733 AN XY: 74442

Gnomad4 AFR AF: 0.0592

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.0166

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.129

Alfa AF: 0.163 Hom.: 2912

Bravo AF: 0.118

Asia WGS AF: 0.0660 AC: 230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.4
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs11770199; hg19: chr7-50685602;