rs4592603

Variant names:

• chr15-48939317-G-A
• rs4592603
• NM_203349.4:c.586-14368C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-48939317-G-A
• chr15-48939317-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_203349.4(SHC4):​c.586-14368C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.948 in 152,270 control chromosomes in the GnomAD database, including 69,379 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 0.95 (69379 hom., cov: 32)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.477
• Publications: 1 publications found

Genes affected

SHC4 (HGNC:16743): (SHC adaptor protein 4) Predicted to enable receptor tyrosine kinase binding activity. Predicted to be involved in transmembrane receptor protein tyrosine kinase signaling pathway. Predicted to act upstream of or within several processes, including apoptotic process; positive regulation of cell population proliferation; and stem cell differentiation. Predicted to be located in postsynaptic membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000259602 (HGNC:):

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 = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHC4	NM_203349.4	c.586-14368C>T		intron_variant	Intron 1 of 11	ENST00000332408.9	NP_976224.3
SHC4	XM_005254375.4	c.36+7243C>T		intron_variant	Intron 1 of 11		XP_005254432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHC4	ENST00000332408.9	c.586-14368C>T		intron_variant	Intron 1 of 11	1	NM_203349.4	ENSP00000329668.4
ENSG00000259602	ENST00000559620.1	n.137+945G>A		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.949 AC: 144327 AN: 152152 Hom.: 69343 Cov.: 32

Gnomad AFR AF: 0.960

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.878

Gnomad ASJ AF: 0.997

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.995

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.996

Gnomad OTH AF: 0.946

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

GnomAD4 genome AF: 0.948 AC: 144418 AN: 152270 Hom.: 69379 Cov.: 32 AF XY: 0.941 AC XY: 70068 AN XY: 74448

African (AFR) AF: 0.960 AC: 39883 AN: 41552

American (AMR) AF: 0.877 AC: 13418 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.997 AC: 3461 AN: 3472

East Asian (EAS) AF: 0.466 AC: 2402 AN: 5156

South Asian (SAS) AF: 0.775 AC: 3733 AN: 4818

European-Finnish (FIN) AF: 0.995 AC: 10573 AN: 10626

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.996 AC: 67758 AN: 68030

Other (OTH) AF: 0.940 AC: 1988 AN: 2114

Alfa AF: 0.976 Hom.: 8470

Bravo AF: 0.938

Asia WGS AF: 0.633 AC: 2204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.40
PhyloP100		0.48
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: rs4592603; hg19: chr15-49231514;