rs739091

Variant names:

• chr22-39921122-C-A
• rs739091
• NM_004810.4:c.-15+19792C>A

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+19792C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,010 control chromosomes in the GnomAD database, including 10,208 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 0.33 (10208 hom., cov: 31)
• Consequence: GRAP2 NM_004810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004810.4. 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
	GRAP2	NM_004810.4	MANE Select	c.-15+19792C>A		intron	N/A	NP_004801.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRAP2	ENST00000344138.9	TSL:1 MANE Select	c.-15+19792C>A		intron	N/A	ENSP00000339186.4

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50402 AN: 151892 Hom.: 10214 Cov.: 31

Gnomad AFR AF: 0.0891

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.332 AC: 50400 AN: 152010 Hom.: 10208 Cov.: 31 AF XY: 0.332 AC XY: 24708 AN XY: 74318

African (AFR) AF: 0.0890 AC: 3691 AN: 41492

American (AMR) AF: 0.431 AC: 6575 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1671 AN: 3472

East Asian (EAS) AF: 0.238 AC: 1229 AN: 5174

South Asian (SAS) AF: 0.348 AC: 1679 AN: 4824

European-Finnish (FIN) AF: 0.420 AC: 4429 AN: 10540

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.439 AC: 29812 AN: 67918

Other (OTH) AF: 0.365 AC: 771 AN: 2112

Alfa AF: 0.414 Hom.: 7140

Bravo AF: 0.326

Asia WGS AF: 0.269 AC: 936 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	0.34
DANN	Benign	0.51
PhyloP100		-1.2
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: rs739091; hg19: chr22-40317126;