22-39911890-C-T

Variant names:

• chr22-39911890-C-T
• rs137967
• NM_004810.4:c.-15+10560C>T

Variant summary

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

The NM_004810.4(GRAP2):​c.-15+10560C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 151,930 control chromosomes in the GnomAD database, including 16,793 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 0.46 (16793 hom., cov: 31)
• Consequence: GRAP2 NM_004810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115
• Publications: 0 publications found

Genes affected

GRAP2 (HGNC:4563): (GRB2 related adaptor protein 2) This gene encodes a member of the GRB2/Sem5/Drk family. This member is an adaptor-like protein involved in leukocyte-specific protein-tyrosine kinase signaling. Like its related family member, GRB2-related adaptor protein (GRAP), this protein contains an SH2 domain flanked by two SH3 domains. This protein interacts with other proteins, such as GRB2-associated binding protein 1 (GAB1) and the SLP-76 leukocyte protein (LCP2), through its SH3 domains. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Apr 2014]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRAP2	NM_004810.4	c.-15+10560C>T		intron_variant	Intron 1 of 7	ENST00000344138.9	NP_004801.1
GRAP2	XM_047441607.1	c.-15+18000C>T		intron_variant	Intron 1 of 7		XP_047297563.1
GRAP2	XM_047441608.1	c.92+10560C>T		intron_variant	Intron 1 of 5		XP_047297564.1
GRAP2	XR_007067995.1	n.247+10560C>T		intron_variant	Intron 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRAP2	ENST00000344138.9	c.-15+10560C>T		intron_variant	Intron 1 of 7	1	NM_004810.4	ENSP00000339186.4

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69069 AN: 151812 Hom.: 16783 Cov.: 31

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.455 AC: 69133 AN: 151930 Hom.: 16793 Cov.: 31 AF XY: 0.454 AC XY: 33707 AN XY: 74234

African (AFR) AF: 0.614 AC: 25429 AN: 41440

American (AMR) AF: 0.431 AC: 6574 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1252 AN: 3472

East Asian (EAS) AF: 0.672 AC: 3456 AN: 5144

South Asian (SAS) AF: 0.479 AC: 2305 AN: 4812

European-Finnish (FIN) AF: 0.326 AC: 3443 AN: 10550

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.371 AC: 25210 AN: 67938

Other (OTH) AF: 0.435 AC: 916 AN: 2108

Alfa AF: 0.397 Hom.: 1555

Bravo AF: 0.467

Asia WGS AF: 0.546 AC: 1899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.74
PhyloP100		-0.12
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: rs137967; hg19: chr22-40307894;