rs2190503

Variant names:

• chr7-50674920-A-G
• rs2190503
• NM_001350814.2:c.140-262T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-50674920-A-G
• chr7-50674920-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001350814.2(GRB10):​c.140-262T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 152,150 control chromosomes in the GnomAD database, including 57,912 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 0.87 (57912 hom., cov: 31)
• Consequence: GRB10 NM_001350814.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.677
• Publications: 7 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350814.2. 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
	GRB10	NM_001350814.2	MANE Select	c.140-262T>C		intron	N/A	NP_001337743.1	Q13322-1
	GRB10	NM_001371009.1		c.287-262T>C		intron	N/A	NP_001357938.1
	GRB10	NM_001350815.2		c.254-262T>C		intron	N/A	NP_001337744.1	A0A2R8YCL1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRB10	ENST00000401949.6	TSL:1 MANE Select	c.140-262T>C		intron	N/A	ENSP00000385770.1	Q13322-1
	GRB10	ENST00000398812.6	TSL:1	c.140-262T>C		intron	N/A	ENSP00000381793.2	Q13322-1
	GRB10	ENST00000357271.9	TSL:1	c.140-262T>C		intron	N/A	ENSP00000349818.5	Q13322-2

Frequencies

GnomAD3 genomes AF: 0.872 AC: 132578 AN: 152032 Hom.: 57882 Cov.: 31

Gnomad AFR AF: 0.849

Gnomad AMI AF: 0.864

Gnomad AMR AF: 0.920

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 0.957

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.850

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.886

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.872 AC: 132666 AN: 152150 Hom.: 57912 Cov.: 31 AF XY: 0.871 AC XY: 64750 AN XY: 74366

African (AFR) AF: 0.849 AC: 35218 AN: 41478

American (AMR) AF: 0.920 AC: 14073 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.906 AC: 3144 AN: 3470

East Asian (EAS) AF: 0.957 AC: 4954 AN: 5178

South Asian (SAS) AF: 0.847 AC: 4079 AN: 4816

European-Finnish (FIN) AF: 0.850 AC: 8999 AN: 10592

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.872 AC: 59270 AN: 68000

Other (OTH) AF: 0.886 AC: 1869 AN: 2110

Alfa AF: 0.875 Hom.: 98257

Bravo AF: 0.878

Asia WGS AF: 0.902 AC: 3138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.2
DANN	Benign	0.33
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2190503; hg19: chr7-50742617;