dbSNP rs2074778: GRB10:c.661+90C>T (chr7-50626732-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001350814.2(GRB10):c.661+90C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 1,438,716 control chromosomes in the GnomAD database, including 80,942 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 0.38 ( 12050 hom., cov: 33)

Exomes 𝑓: 0.32 ( 68892 hom. )

Consequence

GRB10
NM_001350814.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.02

Publications

4 publications found

Variant links:

Genes affected

GRB10 (HGNC:4564): (growth factor receptor bound protein 10) 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. Overexpression of some isoforms of the encoded protein inhibits tyrosine kinase activity and results in growth suppression. This gene is imprinted in a highly isoform- and tissue-specific manner, with expression observed from the paternal allele in the brain, and from the maternal allele in the placental trophoblasts. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2010]

GRB10 links:

Genome browser will be placed here

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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRB10	NM_001350814.2 link	c.661+90C>T		intron_variant	Intron 8 of 18	ENST00000401949.6	NP_001337743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRB10	ENST00000401949.6 link	c.661+90C>T		intron_variant	Intron 8 of 18	1	NM_001350814.2	ENSP00000385770.1		Q13322-1

Frequencies

GnomAD3 genomes

AF:

0.384

AC:

58362

AN:

151994

Hom.:

12030

Cov.:

show subpopulations

Gnomad AFR

AF:

0.540

Gnomad AMI

AF:

0.406

Gnomad AMR

AF:

0.385

Gnomad ASJ

AF:

0.342

Gnomad EAS

AF:

0.361

Gnomad SAS

AF:

0.290

Gnomad FIN

AF:

0.235

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.322

Gnomad OTH

AF:

0.390

GnomAD4 exome

AF:

0.323

AC:

415804

AN:

1286604

Hom.:

68892

AF XY:

0.320

AC XY:

207680

AN XY:

648484

show subpopulations

African (AFR)

AF:

0.546

AC:

16352

AN:

29962

American (AMR)

AF:

0.356

AC:

15807

AN:

44370

Ashkenazi Jewish (ASJ)

AF:

0.344

AC:

8601

AN:

25030

East Asian (EAS)

AF:

0.350

AC:

13596

AN:

38894

South Asian (SAS)

AF:

0.278

AC:

23000

AN:

82660

European-Finnish (FIN)

AF:

0.231

AC:

12227

AN:

53030

Middle Eastern (MID)

AF:

0.295

AC:

1351

AN:

4574

European-Non Finnish (NFE)

AF:

0.322

AC:

306657

AN:

953570

Other (OTH)

AF:

0.334

AC:

18213

AN:

54514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

15030

30060

45091

60121

75151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9490

18980

28470

37960

47450

<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:

0.384

AC:

58427

AN:

152112

Hom.:

12050

Cov.:

AF XY:

0.377

AC XY:

28055

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.540

AC:

22412

AN:

41480

American (AMR)

AF:

0.385

AC:

5890

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.342

AC:

1187

AN:

3470

East Asian (EAS)

AF:

0.360

AC:

1867

AN:

5180

South Asian (SAS)

AF:

0.288

AC:

1386

AN:

4812

European-Finnish (FIN)

AF:

0.235

AC:

2490

AN:

10590

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.322

AC:

21908

AN:

67984

Other (OTH)

AF:

0.393

AC:

829

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1824

3648

5471

7295

9119

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

546

1092

1638

2184

2730

<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:

0.312

Hom.:

2976

Bravo

AF:

0.404

Asia WGS

AF:

0.398

AC:

1382

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.041

(source)

DANN

Benign

0.57

PhyloP100

-1.0

PromoterAI

-0.0023

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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