dbSNP rs138011: GRAP2:c.*1141T>C (chr22-39972225-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.280

Publications

5 publications found

Variant links:

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]

GRAP2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 link	c.*1141T>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000344138.9	NP_004801.1	O75791-1Q6FI14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRAP2	ENST00000344138.9 link	c.*1141T>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_004810.4	ENSP00000339186.4		O75791-1

Frequencies

GnomAD3 genomes

AF:

0.818

AC:

124523

AN:

152170

Hom.:

51631

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.877

AC XY:

AN XY:

106

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.893

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.878

AC:

AN:

Other (OTH)

AF:

0.929

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.818

AC:

124638

AN:

152288

Hom.:

51688

Cov.:

AF XY:

0.814

AC XY:

60636

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.905

AC:

37626

AN:

41570

American (AMR)

AF:

0.667

AC:

10210

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.825

AC:

2864

AN:

3470

East Asian (EAS)

AF:

0.498

AC:

2579

AN:

5178

South Asian (SAS)

AF:

0.752

AC:

3632

AN:

4832

European-Finnish (FIN)

AF:

0.873

AC:

9262

AN:

10612

Middle Eastern (MID)

AF:

0.840

AC:

247

AN:

294

European-Non Finnish (NFE)

AF:

0.820

AC:

55779

AN:

68010

Other (OTH)

AF:

0.801

AC:

1694

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1157

2314

3471

4628

5785

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

876

1752

2628

3504

4380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.811

Hom.:

81046

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

(source)

DANN

Benign

0.51

PhyloP100

-0.28

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over