17-75336713-T-C

Variant names:

• chr17-75336713-T-C
• rs4789170
• NM_002086.5:c.79-3916A>G

Variant summary

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

The NM_002086.5(GRB2):​c.79-3916A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 152,100 control chromosomes in the GnomAD database, including 32,368 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 0.60 (32368 hom., cov: 31)
• Consequence: GRB2 NM_002086.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRB2	NM_002086.5	c.79-3916A>G		intron_variant	Intron 2 of 5	ENST00000316804.10	NP_002077.1
GRB2	NM_203506.3	c.79-3916A>G		intron_variant	Intron 2 of 4		NP_987102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRB2	ENST00000316804.10	c.79-3916A>G		intron_variant	Intron 2 of 5	1	NM_002086.5	ENSP00000339007.4

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90631 AN: 151982 Hom.: 32379 Cov.: 31

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.801

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.866

Gnomad SAS AF: 0.632

Gnomad FIN AF: 0.846

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.596 AC: 90617 AN: 152100 Hom.: 32368 Cov.: 31 AF XY: 0.604 AC XY: 44890 AN XY: 74360

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.682

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.866

Gnomad4 SAS AF: 0.632

Gnomad4 FIN AF: 0.846

Gnomad4 NFE AF: 0.767

Gnomad4 OTH AF: 0.584

Alfa AF: 0.586 Hom.: 2252

Bravo AF: 0.570

Asia WGS AF: 0.641 AC: 2230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.10
DANN	Benign	0.66

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: rs4789170; hg19: chr17-73332794;