Genetic Variant NM_001350814.2:c.846+166A>C (chr7-50617905-T-G) – 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.846+166A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 671,818 control chromosomes in the GnomAD database, including 8,434 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 0.13 ( 1566 hom., cov: 33)

Exomes 𝑓: 0.15 ( 6868 hom. )

Consequence

GRB10
NM_001350814.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.176

Publications

9 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:

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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=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRB10	NM_001350814.2 link	c.846+166A>C		intron_variant	Intron 10 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.846+166A>C		intron_variant	Intron 10 of 18	1	NM_001350814.2	ENSP00000385770.1		Q13322-1

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19854

AN:

152160

Hom.:

1568

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0592

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.0165

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.209

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.179

Gnomad OTH

AF:

0.130

GnomAD4 exome

AF:

0.153

AC:

79260

AN:

519540

Hom.:

6868

Cov.:

AF XY:

0.151

AC XY:

42326

AN XY:

279700

show subpopulations

African (AFR)

AF:

0.0594

AC:

816

AN:

13732

American (AMR)

AF:

0.0981

AC:

2434

AN:

24812

Ashkenazi Jewish (ASJ)

AF:

0.143

AC:

2486

AN:

17336

East Asian (EAS)

AF:

0.0278

AC:

885

AN:

31804

South Asian (SAS)

AF:

0.123

AC:

6705

AN:

54632

European-Finnish (FIN)

AF:

0.214

AC:

7235

AN:

33846

Middle Eastern (MID)

AF:

0.0982

AC:

343

AN:

3494

European-Non Finnish (NFE)

AF:

0.175

AC:

54336

AN:

311114

Other (OTH)

AF:

0.140

AC:

4020

AN:

28770

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

3366

6732

10097

13463

16829

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

322

644

966

1288

1610

<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:

0.130

AC:

19857

AN:

152278

Hom.:

1566

Cov.:

AF XY:

0.131

AC XY:

9733

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0592

AC:

2461

AN:

41564

American (AMR)

AF:

0.103

AC:

1576

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.141

AC:

489

AN:

3470

East Asian (EAS)

AF:

0.0166

AC:

AN:

5192

South Asian (SAS)

AF:

0.104

AC:

501

AN:

4826

European-Finnish (FIN)

AF:

0.209

AC:

2217

AN:

10592

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.179

AC:

12201

AN:

68022

Other (OTH)

AF:

0.129

AC:

273

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

901

1803

2704

3606

4507

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

224

448

672

896

1120

<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:

0.159

Hom.:

3535

Bravo

AF:

0.118

Asia WGS

AF:

0.0660

AC:

230

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.4

(source)

DANN

Benign

0.43

PhyloP100

-0.18

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