rs41282071

Positions:

• chr17-75320799-C-G

Variant summary

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

The NM_002086.5(GRB2):​c.469-246G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0516 in 152,064 control chromosomes in the GnomAD database, including 327 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 0.052 (327 hom., cov: 31)
• Consequence: GRB2 NM_002086.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890

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]

GRB2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRB2	NM_002086.5	c.469-246G>C		intron_variant		ENST00000316804.10	NP_002077.1
GRB2	NM_203506.3	c.346-246G>C		intron_variant			NP_987102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRB2	ENST00000316804.10	c.469-246G>C		intron_variant		1	NM_002086.5	ENSP00000339007.4

Frequencies

GnomAD3 genomes AF: 0.0517 AC: 7851 AN: 151946 Hom.: 328 Cov.: 31

Gnomad AFR AF: 0.0121

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0188

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.0510

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.0620

Gnomad OTH AF: 0.0445

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

GnomAD4 genome AF: 0.0516 AC: 7843 AN: 152064 Hom.: 327 Cov.: 31 AF XY: 0.0544 AC XY: 4039 AN XY: 74308

Gnomad4 AFR AF: 0.0121

Gnomad4 AMR AF: 0.0187

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.0508

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.0620

Gnomad4 OTH AF: 0.0436

Alfa AF: 0.0576 Hom.: 24

Bravo AF: 0.0442

Asia WGS AF: 0.0950 AC: 330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.8
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs41282071; hg19: chr17-73316880;