rs1051160

Positions:

• chr2-164492949-G-A
• chr2-164492949-G-C

Variant summary

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

The NM_004490.3(GRB14):​c.*87C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 1,196,572 control chromosomes in the GnomAD database, including 240,672 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 0.57 (25745 hom., cov: 33)
  • Exomes 𝑓: 0.64 (214927 hom.)
• Consequence: GRB14 NM_004490.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRB14	NM_004490.3	c.*87C>T		3_prime_UTR_variant	14/14	ENST00000263915.8	NP_004481.2
GRB14	NM_001303422.2	c.*87C>T		3_prime_UTR_variant	13/13		NP_001290351.1
GRB14	XM_047444013.1	c.*87C>T		3_prime_UTR_variant	13/13		XP_047299969.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRB14	ENST00000263915.8	c.*87C>T		3_prime_UTR_variant	14/14	1	NM_004490.3	ENSP00000263915
GRB14	ENST00000696453.2	c.*87C>T		3_prime_UTR_variant	13/13			ENSP00000512640	P1
GRB14	ENST00000488342.5	n.1846C>T		non_coding_transcript_exon_variant	14/14	5
GRB14	ENST00000497306.1	n.279C>T		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86494 AN: 151822 Hom.: 25723 Cov.: 33

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.597

GnomAD4 exome AF: 0.635 AC: 663817 AN: 1044632 Hom.: 214927 Cov.: 13 AF XY: 0.633 AC XY: 332023 AN XY: 524300

Gnomad4 AFR exome AF: 0.399

Gnomad4 AMR exome AF: 0.673

Gnomad4 ASJ exome AF: 0.720

Gnomad4 EAS exome AF: 0.348

Gnomad4 SAS exome AF: 0.506

Gnomad4 FIN exome AF: 0.632

Gnomad4 NFE exome AF: 0.662

Gnomad4 OTH exome AF: 0.616

GnomAD4 genome AF: 0.570 AC: 86573 AN: 151940 Hom.: 25745 Cov.: 33 AF XY: 0.566 AC XY: 42027 AN XY: 74278

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.710

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.503

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.657

Gnomad4 OTH AF: 0.597

Alfa AF: 0.620 Hom.: 6059

Bravo AF: 0.564

Asia WGS AF: 0.488 AC: 1696 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.1
DANN	Benign	0.68

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: rs1051160; hg19: chr2-165349459;