rs7800827

Variant names:

• chr7-50605474-C-T
• rs7800827
• NM_001350814.2:c.1273-68G>A

Variant summary

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

The NM_001350814.2(GRB10):​c.1273-68G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00594 in 1,256,084 control chromosomes in the GnomAD database, including 298 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 0.026 (151 hom., cov: 33)
  • Exomes 𝑓: 0.0032 (147 hom.)
• Consequence: GRB10 NM_001350814.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.73
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0876 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.1273-68G>A		intron	N/A	NP_001337743.1	Q13322-1
	GRB10	NM_001371009.1		c.1420-68G>A		intron	N/A	NP_001357938.1
	GRB10	NM_001350815.2		c.1387-68G>A		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.1273-68G>A		intron	N/A	ENSP00000385770.1	Q13322-1
	GRB10	ENST00000398812.6	TSL:1	c.1273-68G>A		intron	N/A	ENSP00000381793.2	Q13322-1
	GRB10	ENST00000357271.9	TSL:1	c.1135-68G>A		intron	N/A	ENSP00000349818.5	Q13322-2

Frequencies

GnomAD3 genomes AF: 0.0260 AC: 3964 AN: 152224 Hom.: 148 Cov.: 33

Gnomad AFR AF: 0.0900

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00981

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.0201

GnomAD4 exome AF: 0.00316 AC: 3488 AN: 1103742 Hom.: 147 AF XY: 0.00272 AC XY: 1539 AN XY: 566190

African (AFR) AF: 0.0905 AC: 2419 AN: 26732

American (AMR) AF: 0.00625 AC: 277 AN: 44296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23830

East Asian (EAS) AF: 0.00 AC: 0 AN: 38066

South Asian (SAS) AF: 0.000227 AC: 18 AN: 79262

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52766

Middle Eastern (MID) AF: 0.00374 AC: 19 AN: 5084

European-Non Finnish (NFE) AF: 0.000526 AC: 413 AN: 785142

Other (OTH) AF: 0.00704 AC: 342 AN: 48564

GnomAD4 genome AF: 0.0261 AC: 3976 AN: 152342 Hom.: 151 Cov.: 33 AF XY: 0.0252 AC XY: 1877 AN XY: 74500

African (AFR) AF: 0.0900 AC: 3742 AN: 41574

American (AMR) AF: 0.00980 AC: 150 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000544 AC: 37 AN: 68032

Other (OTH) AF: 0.0199 AC: 42 AN: 2114

Alfa AF: 0.0147 Hom.: 29

Bravo AF: 0.0297

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.28
DANN	Benign	0.55
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

dbSNP: rs7800827;

hg19: chr7-50673171;