7-50597225-A-G

Variant names:

• chr7-50597225-A-G
• rs12540874
• NM_001350814.2:c.1545-1695T>C

Variant summary

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

The ENST00000401949.6(GRB10):​c.1545-1695T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,178 control chromosomes in the GnomAD database, including 9,259 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 0.33 (9259 hom., cov: 33)
• Consequence: GRB10 ENST00000401949.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.601
• Publications: 34 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000401949.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRB10	NM_001350814.2	MANE Select	c.1545-1695T>C		intron	N/A	NP_001337743.1
	GRB10	NM_001371009.1		c.1692-1695T>C		intron	N/A	NP_001357938.1
	GRB10	NM_001350815.2		c.1659-1695T>C		intron	N/A	NP_001337744.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRB10	ENST00000401949.6	TSL:1 MANE Select	c.1545-1695T>C		intron	N/A	ENSP00000385770.1
	GRB10	ENST00000398812.6	TSL:1	c.1545-1695T>C		intron	N/A	ENSP00000381793.2
	GRB10	ENST00000357271.9	TSL:1	c.1407-1695T>C		intron	N/A	ENSP00000349818.5

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50488 AN: 152060 Hom.: 9255 Cov.: 33

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.332 AC: 50495 AN: 152178 Hom.: 9259 Cov.: 33 AF XY: 0.327 AC XY: 24364 AN XY: 74396

African (AFR) AF: 0.168 AC: 6976 AN: 41538

American (AMR) AF: 0.401 AC: 6125 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1486 AN: 3466

East Asian (EAS) AF: 0.425 AC: 2199 AN: 5178

South Asian (SAS) AF: 0.329 AC: 1583 AN: 4814

European-Finnish (FIN) AF: 0.307 AC: 3250 AN: 10588

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.405 AC: 27562 AN: 67988

Other (OTH) AF: 0.365 AC: 770 AN: 2110

Alfa AF: 0.383 Hom.: 40222

Bravo AF: 0.332

Asia WGS AF: 0.401 AC: 1394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.4
DANN	Benign	0.44
PhyloP100		0.60
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

Other links and lift over

dbSNP: rs12540874; hg19: chr7-50664922;