7-50617905-T-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001350814.2(GRB10):​c.846+166A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000577 in 520,112 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000058 (0 hom.)
• Consequence: GRB10 NM_001350814.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.176
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRB10	NM_001350814.2	c.846+166A>G		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>G		intron_variant	Intron 10 of 18	1	NM_001350814.2	ENSP00000385770.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000577 AC: 3 AN: 520112 Hom.: 0 Cov.: 5 AF XY: 0.00000714 AC XY: 2 AN XY: 280014

African (AFR) AF: 0.00 AC: 0 AN: 13734

American (AMR) AF: 0.00 AC: 0 AN: 24826

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17360

East Asian (EAS) AF: 0.0000943 AC: 3 AN: 31814

South Asian (SAS) AF: 0.00 AC: 0 AN: 54646

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33916

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3496

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 311514

Other (OTH) AF: 0.00 AC: 0 AN: 28806

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.2
DANN	Benign	0.41
PhyloP100		-0.18

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;