rs4423615

Positions:

• chr2-164581720-G-A

Variant summary

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

The NM_004490.3(GRB14):​c.325-33904C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 151,944 control chromosomes in the GnomAD database, including 18,963 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 0.48 (18963 hom., cov: 32)
• Consequence: GRB14 NM_004490.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.598

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRB14	NM_004490.3	c.325-33904C>T		intron_variant		ENST00000263915.8	NP_004481.2
GRB14	XM_011511022.2	c.325-33904C>T		intron_variant			XP_011509324.1
GRB14	XM_047444014.1	c.325-33904C>T		intron_variant			XP_047299970.1
GRB14	XR_427085.4	n.498-33904C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRB14	ENST00000263915.8	c.325-33904C>T		intron_variant		1	NM_004490.3	ENSP00000263915
GRB14	ENST00000446413.6	c.190-33904C>T		intron_variant		1		ENSP00000416786
GRB14	ENST00000424693.1	c.151-33904C>T		intron_variant		4		ENSP00000401702
GRB14	ENST00000488342.5	n.408-33904C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73089 AN: 151826 Hom.: 18950 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.457

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.481 AC: 73151 AN: 151944 Hom.: 18963 Cov.: 32 AF XY: 0.485 AC XY: 35996 AN XY: 74284

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.516

Gnomad4 ASJ AF: 0.560

Gnomad4 EAS AF: 0.366

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.666

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.458

Alfa AF: 0.548 Hom.: 29487

Bravo AF: 0.460

Asia WGS AF: 0.393 AC: 1366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.67

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: rs4423615; hg19: chr2-165438230;