Genetic Variant GRB14:c.1294+9G>A (chr2-164497202-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_004490.3(GRB14):c.1294+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 1,610,620 control chromosomes in the GnomAD database, including 404,642 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 0.70 ( 37717 hom., cov: 32)

Exomes 𝑓: 0.71 ( 366925 hom. )

Consequence

GRB14
NM_004490.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.28

Publications

26 publications found

Variant links:

Genes affected

GRB14 (HGNC:4565): (growth factor receptor bound protein 14) The product of this gene belongs to a small family of adapter proteins that are known to interact with a number of receptor tyrosine kinases and signaling molecules. This gene encodes a growth factor receptor-binding protein that interacts with insulin receptors and insulin-like growth-factor receptors. This protein likely has an inhibitory effect on receptor tyrosine kinase signaling and, in particular, on insulin receptor signaling. This gene may play a role in signaling pathways that regulate growth and metabolism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

GRB14 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=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GRB14	NM_004490.3 link	c.1294+9G>A	intron_variant	Intron 11 of 13	ENST00000263915.8	NP_004481.2
GRB14	NM_001303422.2 link	c.1033+9G>A	intron_variant	Intron 10 of 12		NP_001290351.1	Q14449-2
GRB14	XM_047444013.1 link	c.694+9G>A	intron_variant	Intron 10 of 12		XP_047299969.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRB14	ENST00000263915.8 link	c.1294+9G>A		intron_variant	Intron 11 of 13	1	NM_004490.3	ENSP00000263915.3		Q14449-1

Frequencies

GnomAD3 genomes

AF:

0.701

AC:

106473

AN:

151918

Hom.:

37682

Cov.:

show subpopulations

Gnomad AFR

AF:

0.696

Gnomad AMI

AF:

0.814

Gnomad AMR

AF:

0.717

Gnomad ASJ

AF:

0.756

Gnomad EAS

AF:

0.380

Gnomad SAS

AF:

0.535

Gnomad FIN

AF:

0.747

Gnomad MID

AF:

0.674

Gnomad NFE

AF:

0.725

Gnomad OTH

AF:

0.706

GnomAD2 exomes

AF:

0.674

AC:

168852

AN:

250622

AF XY:

0.668

show subpopulations

Gnomad AFR exome

AF:

0.700

Gnomad AMR exome

AF:

0.709

Gnomad ASJ exome

AF:

0.768

Gnomad EAS exome

AF:

0.356

Gnomad FIN exome

AF:

0.748

Gnomad NFE exome

AF:

0.724

Gnomad OTH exome

AF:

0.704

GnomAD4 exome

AF:

0.705

AC:

1028707

AN:

1458584

Hom.:

366925

Cov.:

AF XY:

0.700

AC XY:

508306

AN XY:

725796

show subpopulations

African (AFR)

AF:

0.699

AC:

23356

AN:

33400

American (AMR)

AF:

0.712

AC:

31800

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.771

AC:

20087

AN:

26070

East Asian (EAS)

AF:

0.379

AC:

15056

AN:

39678

South Asian (SAS)

AF:

0.544

AC:

46867

AN:

86166

European-Finnish (FIN)

AF:

0.746

AC:

39840

AN:

53376

Middle Eastern (MID)

AF:

0.660

AC:

3796

AN:

5750

European-Non Finnish (NFE)

AF:

0.726

AC:

805801

AN:

1109182

Other (OTH)

AF:

0.698

AC:

42104

AN:

60278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

14365

28730

43096

57461

71826

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.701

AC:

106567

AN:

152036

Hom.:

37717

Cov.:

AF XY:

0.696

AC XY:

51704

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.696

AC:

28848

AN:

41448

American (AMR)

AF:

0.717

AC:

10948

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.756

AC:

2626

AN:

3472

East Asian (EAS)

AF:

0.379

AC:

1955

AN:

5154

South Asian (SAS)

AF:

0.536

AC:

2577

AN:

4812

European-Finnish (FIN)

AF:

0.747

AC:

7912

AN:

10586

Middle Eastern (MID)

AF:

0.667

AC:

196

AN:

294

European-Non Finnish (NFE)

AF:

0.725

AC:

49272

AN:

67972

Other (OTH)

AF:

0.705

AC:

1491

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1609

3219

4828

6438

8047

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.712

Hom.:

74130

Bravo

AF:

0.698

Asia WGS

AF:

0.529

AC:

1841

AN:

3476

EpiCase

AF:

0.722

EpiControl

AF:

0.717

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.24

(source)

DANN

Benign

0.62

PhyloP100

-1.3

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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2-164497202-C-T

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