rs138011

Variant names:

• chr22-39972225-T-C
• rs138011
• NM_004810.4:c.*1141T>C

Variant summary

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

The NM_004810.4(GRAP2):​c.*1141T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 152,440 control chromosomes in the GnomAD database, including 51,748 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 0.82 (51688 hom., cov: 35)
  • Exomes 𝑓: 0.89 (60 hom.)
• Consequence: GRAP2 NM_004810.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRAP2	NM_004810.4	c.*1141T>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000344138.9	NP_004801.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRAP2	ENST00000344138.9	c.*1141T>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_004810.4	ENSP00000339186.4

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124523 AN: 152170 Hom.: 51631 Cov.: 35

Gnomad AFR AF: 0.905

Gnomad AMI AF: 0.817

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.751

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.800

GnomAD4 exome AF: 0.888 AC: 135 AN: 152 Hom.: 60 Cov.: 0 AF XY: 0.877 AC XY: 93 AN XY: 106

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.893

Gnomad4 NFE exome AF: 0.878

Gnomad4 OTH exome AF: 0.929

GnomAD4 genome AF: 0.818 AC: 124638 AN: 152288 Hom.: 51688 Cov.: 35 AF XY: 0.814 AC XY: 60636 AN XY: 74462

Gnomad4 AFR AF: 0.905

Gnomad4 AMR AF: 0.667

Gnomad4 ASJ AF: 0.825

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.752

Gnomad4 FIN AF: 0.873

Gnomad4 NFE AF: 0.820

Gnomad4 OTH AF: 0.801

Alfa AF: 0.812 Hom.: 63449

Bravo AF: 0.803

Asia WGS AF: 0.665 AC: 2317 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	2.1
DANN	Benign	0.51

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: rs138011; hg19: chr22-40368229;