7-50687817-T-G

Variant names:

• chr7-50687817-T-G
• rs2282931
• NM_001350814.2:c.140-13159A>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.140-13159A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 152,088 control chromosomes in the GnomAD database, including 17,665 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 0.47 (17665 hom., cov: 33)
• Consequence: GRB10 NM_001350814.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRB10	NM_001350814.2	c.140-13159A>C		intron_variant	Intron 5 of 18	ENST00000401949.6	NP_001337743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRB10	ENST00000401949.6	c.140-13159A>C		intron_variant	Intron 5 of 18	1	NM_001350814.2	ENSP00000385770.1

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71477 AN: 151970 Hom.: 17662 Cov.: 33

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.518

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.470 AC: 71503 AN: 152088 Hom.: 17665 Cov.: 33 AF XY: 0.465 AC XY: 34584 AN XY: 74334

African (AFR) AF: 0.320 AC: 13286 AN: 41476

American (AMR) AF: 0.553 AC: 8447 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1820 AN: 3472

East Asian (EAS) AF: 0.398 AC: 2062 AN: 5178

South Asian (SAS) AF: 0.484 AC: 2333 AN: 4824

European-Finnish (FIN) AF: 0.410 AC: 4332 AN: 10560

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.551 AC: 37436 AN: 67974

Other (OTH) AF: 0.518 AC: 1093 AN: 2112

Alfa AF: 0.495 Hom.: 8729

Bravo AF: 0.469

Asia WGS AF: 0.518 AC: 1805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.13
DANN	Benign	0.32
PhyloP100		-1.1
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: rs2282931; hg19: chr7-50755514;