rs4592603

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SHC4	NM_203349.4	c.586-14368C>T		intron_variant		ENST00000332408.9	NP_976224.3
SHC4	XM_005254375.4	c.36+7243C>T		intron_variant			XP_005254432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHC4	ENST00000332408.9	c.586-14368C>T		intron_variant		1	NM_203349.4	ENSP00000329668.4
ENSG00000259602	ENST00000559620.1	n.137+945G>A		intron_variant		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

Gnomad4 AFR AF: 0.960

Gnomad4 AMR AF: 0.877

Gnomad4 ASJ AF: 0.997

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.775

Gnomad4 FIN AF: 0.995

Gnomad4 NFE AF: 0.996

Gnomad4 OTH AF: 0.940

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

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: rs4592603; hg19: chr15-49231514;