rs4259993

chr15-48932175-G-Achr15-48932175-G-T

Variant summary

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

The NM_203349.4(SHC4):c.586-7226C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 151,800 control chromosomes in the GnomAD database, including 2,516 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 0.18 (2516 hom., cov: 31)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.488

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHC4	NM_203349.4	c.586-7226C>T		intron_variant		ENST00000332408.9
SHC4	XM_005254375.4	c.37-7226C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHC4	ENST00000332408.9	c.586-7226C>T		intron_variant		1	NM_203349.4	P1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26722 AN: 151682 Hom.: 2516 Cov.: 31

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.176 AC: 26739 AN: 151800 Hom.: 2516 Cov.: 31 AF XY: 0.180 AC XY: 13363 AN XY: 74172

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.170

Alfa AF: 0.173 Hom.: 1697

Bravo AF: 0.163

Asia WGS AF: 0.248 AC: 860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.62
Dann	Benign	0.51

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: rs4259993; hg19: chr15-49224372;