rs6945597

Positions:

• chr7-50771230-T-A
• chr7-50771230-T-C

Variant summary

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

The NM_001350814.2(GRB10):​c.-217+9397A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 152,030 control chromosomes in the GnomAD database, including 31,969 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 0.62 (31969 hom., cov: 32)
• Consequence: GRB10 NM_001350814.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.434

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]

GRB10 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRB10	NM_001350814.2	c.-217+9397A>T		intron_variant		ENST00000401949.6	NP_001337743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRB10	ENST00000401949.6	c.-217+9397A>T		intron_variant		1	NM_001350814.2	ENSP00000385770.1

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94141 AN: 151912 Hom.: 31973 Cov.: 32

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.811

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.619 AC: 94146 AN: 152030 Hom.: 31969 Cov.: 32 AF XY: 0.611 AC XY: 45370 AN XY: 74312

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.811

Gnomad4 EAS AF: 0.707

Gnomad4 SAS AF: 0.703

Gnomad4 FIN AF: 0.571

Gnomad4 NFE AF: 0.773

Gnomad4 OTH AF: 0.688

Alfa AF: 0.682 Hom.: 4635

Bravo AF: 0.606

Asia WGS AF: 0.724 AC: 2518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.43
DANN	Benign	0.46

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6945597; hg19: chr7-50838927;