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

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

Gnomad4 AFR exome

AF:

0.699

AC:

23356

AN:

33400

Gnomad4 AMR exome

AF:

0.712

AC:

31800

AN:

44684

Gnomad4 ASJ exome

AF:

0.771

AC:

20087

AN:

26070

Gnomad4 EAS exome

AF:

0.379

AC:

15056

AN:

39678

Gnomad4 SAS exome

AF:

0.544

AC:

46867

AN:

86166

Gnomad4 FIN exome

AF:

0.746

AC:

39840

AN:

53376

Gnomad4 NFE exome

AF:

0.726

AC:

805801

AN:

1109182

Gnomad4 Remaining exome

AF:

0.698

AC:

42104

AN:

60278

Heterozygous variant carriers

14365

28730

43096

57461

71826

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

19830

39660

59490

79320

99150

<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:

0.701

AC:

106567

AN:

152036

Hom.:

37717

Cov.:

AF XY:

0.696

AC XY:

51704

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.696

AC:

0.696005

AN:

0.696005

Gnomad4 AMR

AF:

0.717

AC:

0.716961

AN:

0.716961

Gnomad4 ASJ

AF:

0.756

AC:

0.756336

AN:

0.756336

Gnomad4 EAS

AF:

0.379

AC:

0.379317

AN:

0.379317

Gnomad4 SAS

AF:

0.536

AC:

0.535536

AN:

0.535536

Gnomad4 FIN

AF:

0.747

AC:

0.747402

AN:

0.747402

Gnomad4 NFE

AF:

0.725

AC:

0.724887

AN:

0.724887

Gnomad4 OTH

AF:

0.705

AC:

0.704631

AN:

0.704631

Heterozygous variant carriers

1609

3219

4828

6438

8047

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

816

1632

2448

3264

4080

<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:

0.712

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

DANN

Benign

0.62

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over