2-164497202-C-T

Position:

• chr2-164497202-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004490.3(GRB14):​c.1294+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 1,610,620 control chromosomes in the GnomAD database, including 404,642 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 0.70 (37717 hom., cov: 32)
  • Exomes 𝑓: 0.71 (366925 hom.)
• Consequence: GRB14 NM_004490.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

Genes affected

GRB14 (HGNC:4565): (growth factor receptor bound protein 14) 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. This protein likely has an inhibitory effect on receptor tyrosine kinase signaling and, in particular, on insulin receptor signaling. This gene may play a role in signaling pathways that regulate growth and metabolism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

GRB14 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRB14	NM_004490.3	c.1294+9G>A		intron_variant		ENST00000263915.8	NP_004481.2
GRB14	NM_001303422.2	c.1033+9G>A		intron_variant			NP_001290351.1
GRB14	XM_047444013.1	c.694+9G>A		intron_variant			XP_047299969.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRB14	ENST00000263915.8	c.1294+9G>A		intron_variant		1	NM_004490.3	ENSP00000263915.3
GRB14	ENST00000446413.6	c.1159+9G>A		intron_variant		1		ENSP00000416786.2
GRB14	ENST00000696453.2	c.1033+9G>A		intron_variant				ENSP00000512640.1
GRB14	ENST00000488342.5	n.1430+9G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106473 AN: 151918 Hom.: 37682 Cov.: 32

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.706

GnomAD3 exomes AF: 0.674 AC: 168852 AN: 250622 Hom.: 58466 AF XY: 0.668 AC XY: 90473 AN XY: 135430

Gnomad AFR exome AF: 0.700

Gnomad AMR exome AF: 0.709

Gnomad ASJ exome AF: 0.768

Gnomad EAS exome AF: 0.356

Gnomad SAS exome AF: 0.535

Gnomad FIN exome AF: 0.748

Gnomad NFE exome AF: 0.724

Gnomad OTH exome AF: 0.704

GnomAD4 exome AF: 0.705 AC: 1028707 AN: 1458584 Hom.: 366925 Cov.: 33 AF XY: 0.700 AC XY: 508306 AN XY: 725796

Gnomad4 AFR exome AF: 0.699

Gnomad4 AMR exome AF: 0.712

Gnomad4 ASJ exome AF: 0.771

Gnomad4 EAS exome AF: 0.379

Gnomad4 SAS exome AF: 0.544

Gnomad4 FIN exome AF: 0.746

Gnomad4 NFE exome AF: 0.726

Gnomad4 OTH exome AF: 0.698

GnomAD4 genome AF: 0.701 AC: 106567 AN: 152036 Hom.: 37717 Cov.: 32 AF XY: 0.696 AC XY: 51704 AN XY: 74314

Gnomad4 AFR AF: 0.696

Gnomad4 AMR AF: 0.717

Gnomad4 ASJ AF: 0.756

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.747

Gnomad4 NFE AF: 0.725

Gnomad4 OTH AF: 0.705

Alfa AF: 0.715 Hom.: 20496

Bravo AF: 0.698

Asia WGS AF: 0.529 AC: 1841 AN: 3476

EpiCase AF: 0.722

EpiControl AF: 0.717

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.24
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs8192673; hg19: chr2-165353712; COSMIC: COSV55735865; COSMIC: COSV55735865;