NM_004490.3:c.1294+9G>A

Variant names:

• chr2-164497202-C-T
• rs8192673
• NM_004490.3:c.1294+9G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 26 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004490.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRB14	NM_004490.3	MANE Select	c.1294+9G>A		intron	N/A	NP_004481.2	Q14449-1
	GRB14	NM_001303422.2		c.1033+9G>A		intron	N/A	NP_001290351.1	Q14449-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRB14	ENST00000263915.8	TSL:1 MANE Select	c.1294+9G>A		intron	N/A	ENSP00000263915.3	Q14449-1
	GRB14	ENST00000446413.6	TSL:1	c.1159+9G>A		intron	N/A	ENSP00000416786.2	C9JD37
	GRB14	ENST00000943514.1		c.1453+9G>A		intron	N/A	ENSP00000613573.1

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

GnomAD2 exomes AF: 0.674 AC: 168852 AN: 250622 AF XY: 0.668

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 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

African (AFR) AF: 0.699 AC: 23356 AN: 33400

American (AMR) AF: 0.712 AC: 31800 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.771 AC: 20087 AN: 26070

East Asian (EAS) AF: 0.379 AC: 15056 AN: 39678

South Asian (SAS) AF: 0.544 AC: 46867 AN: 86166

European-Finnish (FIN) AF: 0.746 AC: 39840 AN: 53376

Middle Eastern (MID) AF: 0.660 AC: 3796 AN: 5750

European-Non Finnish (NFE) AF: 0.726 AC: 805801 AN: 1109182

Other (OTH) AF: 0.698 AC: 42104 AN: 60278

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

African (AFR) AF: 0.696 AC: 28848 AN: 41448

American (AMR) AF: 0.717 AC: 10948 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 2626 AN: 3472

East Asian (EAS) AF: 0.379 AC: 1955 AN: 5154

South Asian (SAS) AF: 0.536 AC: 2577 AN: 4812

European-Finnish (FIN) AF: 0.747 AC: 7912 AN: 10586

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.725 AC: 49272 AN: 67972

Other (OTH) AF: 0.705 AC: 1491 AN: 2116

Alfa AF: 0.712 Hom.: 74130

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.24
DANN	Benign	0.62
PhyloP100		-1.3
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: rs8192673; hg19: chr2-165353712; COSMIC: COSV55735865; COSMIC: COSV55735865;