7-50717751-C-T

Variant names:

• chr7-50717751-C-T
• rs1978208
• NM_001350814.2:c.52-13843G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001350814.2(GRB10):​c.52-13843G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 152,154 control chromosomes in the GnomAD database, including 41,783 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 0.72 (41783 hom., cov: 33)
• Consequence: GRB10 NM_001350814.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.828 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRB10	NM_001350814.2	MANE Select	c.52-13843G>A		intron	N/A	NP_001337743.1
	GRB10	NM_001371009.1		c.286+38136G>A		intron	N/A	NP_001357938.1
	GRB10	NM_001350815.2		c.253+38136G>A		intron	N/A	NP_001337744.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRB10	ENST00000401949.6	TSL:1 MANE Select	c.52-13843G>A		intron	N/A	ENSP00000385770.1
	GRB10	ENST00000398812.6	TSL:1	c.52-13843G>A		intron	N/A	ENSP00000381793.2
	GRB10	ENST00000357271.9	TSL:1	c.52-13843G>A		intron	N/A	ENSP00000349818.5

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109800 AN: 152036 Hom.: 41776 Cov.: 33

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.852

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.834

Gnomad OTH AF: 0.759

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

GnomAD4 genome AF: 0.722 AC: 109835 AN: 152154 Hom.: 41783 Cov.: 33 AF XY: 0.725 AC XY: 53905 AN XY: 74388

African (AFR) AF: 0.456 AC: 18896 AN: 41470

American (AMR) AF: 0.801 AC: 12255 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.852 AC: 2955 AN: 3470

East Asian (EAS) AF: 0.748 AC: 3864 AN: 5168

South Asian (SAS) AF: 0.826 AC: 3983 AN: 4824

European-Finnish (FIN) AF: 0.808 AC: 8563 AN: 10594

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.834 AC: 56700 AN: 68018

Other (OTH) AF: 0.759 AC: 1602 AN: 2110

Alfa AF: 0.807 Hom.: 27650

Bravo AF: 0.707

Asia WGS AF: 0.798 AC: 2774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.1
DANN	Benign	0.81
PhyloP100		-0.21
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: rs1978208; hg19: chr7-50785448;