7-50617905-T-G

Variant names:

• chr7-50617905-T-G
• rs11770199
• NM_001350814.2:c.846+166A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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=-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 rank	MANE	Protein	UniProt
GRB10	NM_001350814.2	c.846+166A>C		intron_variant	Intron 10 of 18	ENST00000401949.6	NP_001337743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRB10	ENST00000401949.6	c.846+166A>C		intron_variant	Intron 10 of 18	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

African (AFR) AF: 0.0594 AC: 816 AN: 13732

American (AMR) AF: 0.0981 AC: 2434 AN: 24812

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 2486 AN: 17336

East Asian (EAS) AF: 0.0278 AC: 885 AN: 31804

South Asian (SAS) AF: 0.123 AC: 6705 AN: 54632

European-Finnish (FIN) AF: 0.214 AC: 7235 AN: 33846

Middle Eastern (MID) AF: 0.0982 AC: 343 AN: 3494

European-Non Finnish (NFE) AF: 0.175 AC: 54336 AN: 311114

Other (OTH) AF: 0.140 AC: 4020 AN: 28770

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

African (AFR) AF: 0.0592 AC: 2461 AN: 41564

American (AMR) AF: 0.103 AC: 1576 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 489 AN: 3470

East Asian (EAS) AF: 0.0166 AC: 86 AN: 5192

South Asian (SAS) AF: 0.104 AC: 501 AN: 4826

European-Finnish (FIN) AF: 0.209 AC: 2217 AN: 10592

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12201 AN: 68022

Other (OTH) AF: 0.129 AC: 273 AN: 2114

Alfa AF: 0.159 Hom.: 3535

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
PhyloP100		-0.18
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: rs11770199; hg19: chr7-50685602; COSMIC: COSV107416469;