7-50626732-G-C

Variant names:

• chr7-50626732-G-C
• rs2074778
• NM_001350814.2:c.661+90C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001350814.2(GRB10):​c.661+90C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000931 in 1,289,398 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000093 (0 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BS2: High AC in GnomAdExome4 at 12 AD gene.

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>G		intron	N/A	NP_001337743.1
	GRB10	NM_001371009.1		c.808+90C>G		intron	N/A	NP_001357938.1
	GRB10	NM_001350815.2		c.775+90C>G		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>G		intron	N/A	ENSP00000385770.1
	GRB10	ENST00000398812.6	TSL:1	c.661+90C>G		intron	N/A	ENSP00000381793.2
	GRB10	ENST00000357271.9	TSL:1	c.661+90C>G		intron	N/A	ENSP00000349818.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000931 AC: 12 AN: 1289398 Hom.: 0 AF XY: 0.00000923 AC XY: 6 AN XY: 649812

African (AFR) AF: 0.00 AC: 0 AN: 29994

American (AMR) AF: 0.0000225 AC: 1 AN: 44380

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25046

East Asian (EAS) AF: 0.00 AC: 0 AN: 38902

South Asian (SAS) AF: 0.00 AC: 0 AN: 82714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53056

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4590

European-Non Finnish (NFE) AF: 0.0000115 AC: 11 AN: 956120

Other (OTH) AF: 0.00 AC: 0 AN: 54596

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 2976

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.017
DANN	Benign	0.49
PhyloP100		-1.0
PromoterAI		0.033	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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;