17-75356787-A-T

Variant names:

• chr17-75356787-A-T
• rs4789176
• NM_002086.5:c.79-23990T>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.79-23990T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 152,068 control chromosomes in the GnomAD database, including 39,033 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 0.66 (39033 hom., cov: 31)
• Consequence: GRB2 NM_002086.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.320
• Publications: 8 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 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.79-23990T>A		intron	N/A	NP_002077.1
	GRB2	NM_203506.3		c.79-23990T>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.79-23990T>A		intron	N/A	ENSP00000339007.4
	GRB2	ENST00000392564.5	TSL:1	c.79-23990T>A		intron	N/A	ENSP00000376347.1
	GRB2	ENST00000392563.5	TSL:1	c.79-23990T>A		intron	N/A	ENSP00000376346.1

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100847 AN: 151950 Hom.: 39046 Cov.: 31

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.898

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.673

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

GnomAD4 genome AF: 0.663 AC: 100839 AN: 152068 Hom.: 39033 Cov.: 31 AF XY: 0.671 AC XY: 49908 AN XY: 74368

African (AFR) AF: 0.235 AC: 9719 AN: 41424

American (AMR) AF: 0.740 AC: 11295 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 2529 AN: 3468

East Asian (EAS) AF: 0.909 AC: 4703 AN: 5176

South Asian (SAS) AF: 0.742 AC: 3579 AN: 4824

European-Finnish (FIN) AF: 0.898 AC: 9523 AN: 10602

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.840 AC: 57144 AN: 67998

Other (OTH) AF: 0.670 AC: 1417 AN: 2114

Alfa AF: 0.747 Hom.: 5755

Bravo AF: 0.634

Asia WGS AF: 0.729 AC: 2537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.9
DANN	Benign	0.72
PhyloP100		0.32
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: rs4789176; hg19: chr17-73352868;