chr7-50626732-G-A

Variant names:

• chr7-50626732-G-A
• rs2074778
• NM_001350814.2:c.661+90C>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.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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.534 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRB10	NM_001350814.2	MANE Select	c.661+90C>T		intron	N/A	NP_001337743.1
	GRB10	NM_001371009.1		c.808+90C>T		intron	N/A	NP_001357938.1
	GRB10	NM_001350815.2		c.775+90C>T		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.661+90C>T		intron	N/A	ENSP00000385770.1
	GRB10	ENST00000398812.6	TSL:1	c.661+90C>T		intron	N/A	ENSP00000381793.2
	GRB10	ENST00000357271.9	TSL:1	c.661+90C>T		intron	N/A	ENSP00000349818.5

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58362 AN: 151994 Hom.: 12030 Cov.: 33

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

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

GnomAD4 genome AF: 0.384 AC: 58427 AN: 152112 Hom.: 12050 Cov.: 33 AF XY: 0.377 AC XY: 28055 AN XY: 74394

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: 89 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21908 AN: 67984

Other (OTH) AF: 0.393 AC: 829 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.041
DANN	Benign	0.57
PhyloP100		-1.0
PromoterAI		-0.0023	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2074778; hg19: chr7-50694429;