17-75345631-C-T

Variant names:

• chr17-75345631-C-T
• rs4789172
• NM_002086.5:c.79-12834G>A

Variant summary

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

The NM_002086.5(GRB2):​c.79-12834G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,944 control chromosomes in the GnomAD database, including 13,082 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 0.37 (13082 hom., cov: 30)
• Consequence: GRB2 NM_002086.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 19 publications found

Genes affected

GRB2 (HGNC:4566): (growth factor receptor bound protein 2) The protein encoded by this gene binds the epidermal growth factor receptor and contains one SH2 domain and two SH3 domains. Its two SH3 domains direct complex formation with proline-rich regions of other proteins, and its SH2 domain binds tyrosine phosphorylated sequences. This gene is similar to the Sem5 gene of C.elegans, which is involved in the signal transduction pathway. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ENSG00000265987 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002086.5. 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
	GRB2	NM_002086.5	MANE Select	c.79-12834G>A		intron	N/A	NP_002077.1
	GRB2	NM_203506.3		c.79-12834G>A		intron	N/A	NP_987102.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRB2	ENST00000316804.10	TSL:1 MANE Select	c.79-12834G>A		intron	N/A	ENSP00000339007.4
	GRB2	ENST00000392564.5	TSL:1	c.79-12834G>A		intron	N/A	ENSP00000376347.1
	GRB2	ENST00000392563.5	TSL:1	c.79-12834G>A		intron	N/A	ENSP00000376346.1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56233 AN: 151826 Hom.: 13086 Cov.: 30

Gnomad AFR AF: 0.0993

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.370 AC: 56206 AN: 151944 Hom.: 13082 Cov.: 30 AF XY: 0.368 AC XY: 27316 AN XY: 74254

African (AFR) AF: 0.0990 AC: 4105 AN: 41476

American (AMR) AF: 0.332 AC: 5069 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1420 AN: 3462

East Asian (EAS) AF: 0.225 AC: 1167 AN: 5184

South Asian (SAS) AF: 0.319 AC: 1535 AN: 4814

European-Finnish (FIN) AF: 0.516 AC: 5438 AN: 10534

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.531 AC: 36055 AN: 67914

Other (OTH) AF: 0.352 AC: 741 AN: 2108

Alfa AF: 0.486 Hom.: 18079

Bravo AF: 0.343

Asia WGS AF: 0.249 AC: 868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.55
DANN	Benign	0.71
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: rs4789172; hg19: chr17-73341712; COSMIC: COSV57306837;