2-164492949-G-C

Variant names:

• chr2-164492949-G-C
• rs1051160
• NM_004490.3:c.*87C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004490.3(GRB14):​c.*87C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000955 in 1,047,414 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: 9.5e-7 (0 hom.)
• Consequence: GRB14 NM_004490.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• Publications: 9 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRB14	NM_004490.3	MANE Select	c.*87C>G		3_prime_UTR	Exon 14 of 14	NP_004481.2
	GRB14	NM_001303422.2		c.*87C>G		3_prime_UTR	Exon 13 of 13	NP_001290351.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRB14	ENST00000263915.8	TSL:1 MANE Select	c.*87C>G		3_prime_UTR	Exon 14 of 14	ENSP00000263915.3
	GRB14	ENST00000488342.5	TSL:5	n.1846C>G		non_coding_transcript_exon	Exon 14 of 14
	GRB14	ENST00000497306.1	TSL:3	n.279C>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.55e-7 AC: 1 AN: 1047414 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 525714

African (AFR) AF: 0.00 AC: 0 AN: 23300

American (AMR) AF: 0.00 AC: 0 AN: 24562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17950

East Asian (EAS) AF: 0.00 AC: 0 AN: 34598

South Asian (SAS) AF: 0.00 AC: 0 AN: 52462

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4658

European-Non Finnish (NFE) AF: 0.00000125 AC: 1 AN: 801232

Other (OTH) AF: 0.00 AC: 0 AN: 44824

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 11964

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.3
DANN	Benign	0.73
PhyloP100		0.074

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: rs1051160; hg19: chr2-165349459;