chr7-50779949-G-A

Variant names:

• chr7-50779949-G-A
• rs1014384
• NM_001350814.2:c.-217+678C>T

Variant summary

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

The NM_001350814.2(GRB10):​c.-217+678C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 151,988 control chromosomes in the GnomAD database, including 30,542 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 (30542 hom., cov: 32)
• Consequence: GRB10 NM_001350814.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.732 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.-217+678C>T		intron	N/A	NP_001337743.1
	GRB10	NM_001371009.1		c.116+2475C>T		intron	N/A	NP_001357938.1
	GRB10	NM_001350815.2		c.83+12493C>T		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.-217+678C>T		intron	N/A	ENSP00000385770.1
	GRB10	ENST00000335866.7	TSL:1	c.-294+13275C>T		intron	N/A	ENSP00000338543.3
	GRB10	ENST00000407526.6	TSL:1	c.-478+2475C>T		intron	N/A	ENSP00000385046.1

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93492 AN: 151868 Hom.: 30542 Cov.: 32

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.796

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.673

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

GnomAD4 genome AF: 0.615 AC: 93505 AN: 151988 Hom.: 30542 Cov.: 32 AF XY: 0.607 AC XY: 45074 AN XY: 74264

African (AFR) AF: 0.397 AC: 16454 AN: 41442

American (AMR) AF: 0.588 AC: 8980 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 2643 AN: 3466

East Asian (EAS) AF: 0.712 AC: 3681 AN: 5170

South Asian (SAS) AF: 0.657 AC: 3164 AN: 4816

European-Finnish (FIN) AF: 0.579 AC: 6110 AN: 10546

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.738 AC: 50130 AN: 67950

Other (OTH) AF: 0.676 AC: 1426 AN: 2108

Alfa AF: 0.718 Hom.: 32003

Bravo AF: 0.603

Asia WGS AF: 0.714 AC: 2485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.9
DANN	Benign	0.76
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1014384; hg19: chr7-50847646;