chr15-48935624-C-T

Variant names:

• chr15-48935624-C-T
• rs4491452
• NM_203349.4:c.586-10675G>A

Variant summary

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

The NM_203349.4(SHC4):​c.586-10675G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 152,098 control chromosomes in the GnomAD database, including 51,345 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 0.82 (51345 hom., cov: 32)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHC4	NM_203349.4	c.586-10675G>A		intron_variant	Intron 1 of 11	ENST00000332408.9	NP_976224.3
SHC4	XM_005254375.4	c.37-10675G>A		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.586-10675G>A		intron_variant	Intron 1 of 11	1	NM_203349.4	ENSP00000329668.4

Frequencies

GnomAD3 genomes AF: 0.821 AC: 124764 AN: 151980 Hom.: 51291 Cov.: 32

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.895

Gnomad EAS AF: 0.926

Gnomad SAS AF: 0.880

Gnomad FIN AF: 0.790

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.825

Gnomad OTH AF: 0.845

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

GnomAD4 genome AF: 0.821 AC: 124875 AN: 152098 Hom.: 51345 Cov.: 32 AF XY: 0.819 AC XY: 60906 AN XY: 74352

African (AFR) AF: 0.807 AC: 33503 AN: 41494

American (AMR) AF: 0.784 AC: 11966 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.895 AC: 3105 AN: 3470

East Asian (EAS) AF: 0.926 AC: 4795 AN: 5178

South Asian (SAS) AF: 0.880 AC: 4244 AN: 4820

European-Finnish (FIN) AF: 0.790 AC: 8348 AN: 10568

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.825 AC: 56111 AN: 67990

Other (OTH) AF: 0.845 AC: 1784 AN: 2112

Alfa AF: 0.827 Hom.: 218252

Bravo AF: 0.821

Asia WGS AF: 0.899 AC: 3127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.6
DANN	Benign	0.46
PhyloP100		0.062
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: rs4491452; hg19: chr15-49227821;