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

27 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:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_004490.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004490.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRB14	NM_004490.3	MANE Select	c.1294+9G>A		intron	N/A	NP_004481.2	Q14449-1
	GRB14	NM_001303422.2		c.1033+9G>A		intron	N/A	NP_001290351.1	Q14449-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GRB14	ENST00000263915.8	TSL:1 MANE Select	c.1294+9G>A	intron	N/A	ENSP00000263915.3	Q14449-1
GRB14	ENST00000446413.6	TSL:1	c.1159+9G>A	intron	N/A	ENSP00000416786.2	C9JD37
GRB14	ENST00000943514.1		c.1453+9G>A	intron	N/A	ENSP00000613573.1

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

Age Distribution

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

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

Age Distribution

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over