7-50683393-T-C

Position:

• chr7-50683393-T-C

Variant summary

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

The ENST00000401949.6(GRB10):​c.140-8735A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 152,128 control chromosomes in the GnomAD database, including 40,598 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 (40598 hom., cov: 32)
• Consequence: GRB10 ENST00000401949.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRB10	NM_001350814.2	c.140-8735A>G		intron_variant		ENST00000401949.6	NP_001337743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRB10	ENST00000401949.6	c.140-8735A>G		intron_variant		1	NM_001350814.2	ENSP00000385770	P3

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109626 AN: 152010 Hom.: 40594 Cov.: 32

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.817

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.907

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.876

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.783

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

GnomAD4 genome AF: 0.721 AC: 109663 AN: 152128 Hom.: 40598 Cov.: 32 AF XY: 0.714 AC XY: 53123 AN XY: 74368

Gnomad4 AFR AF: 0.566

Gnomad4 AMR AF: 0.817

Gnomad4 ASJ AF: 0.876

Gnomad4 EAS AF: 0.907

Gnomad4 SAS AF: 0.723

Gnomad4 FIN AF: 0.603

Gnomad4 NFE AF: 0.786

Gnomad4 OTH AF: 0.784

Alfa AF: 0.793 Hom.: 109577

Bravo AF: 0.730

Asia WGS AF: 0.812 AC: 2823 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.76
DANN	Benign	0.42

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: rs10248619; hg19: chr7-50751090;