rs10519195

Variant names:

• chr15-48870987-C-T
• rs10519195
• NM_203349.4:c.894+1102G>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.894+1102G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0534 in 152,200 control chromosomes in the GnomAD database, including 405 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 0.053 (405 hom., cov: 33)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.427
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHC4	NM_203349.4	c.894+1102G>A		intron_variant	Intron 5 of 11	ENST00000332408.9	NP_976224.3
SHC4	XM_005254375.4	c.345+1102G>A		intron_variant	Intron 5 of 11		XP_005254432.1
SHC4	XM_047432492.1	c.36+1102G>A		intron_variant	Intron 2 of 8		XP_047288448.1
SHC4	XM_047432493.1	c.36+1102G>A		intron_variant	Intron 3 of 9		XP_047288449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHC4	ENST00000332408.9	c.894+1102G>A		intron_variant	Intron 5 of 11	1	NM_203349.4	ENSP00000329668.4

Frequencies

GnomAD3 genomes AF: 0.0534 AC: 8115 AN: 152082 Hom.: 403 Cov.: 33

Gnomad AFR AF: 0.0916

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0445

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.0333

Gnomad FIN AF: 0.0698

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0211

Gnomad OTH AF: 0.0473

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

GnomAD4 genome AF: 0.0534 AC: 8131 AN: 152200 Hom.: 405 Cov.: 33 AF XY: 0.0547 AC XY: 4070 AN XY: 74418

African (AFR) AF: 0.0917 AC: 3805 AN: 41494

American (AMR) AF: 0.0446 AC: 683 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 45 AN: 3470

East Asian (EAS) AF: 0.223 AC: 1153 AN: 5174

South Asian (SAS) AF: 0.0331 AC: 160 AN: 4830

European-Finnish (FIN) AF: 0.0698 AC: 740 AN: 10608

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0211 AC: 1436 AN: 68002

Other (OTH) AF: 0.0487 AC: 103 AN: 2114

Alfa AF: 0.0329 Hom.: 237

Bravo AF: 0.0547

Asia WGS AF: 0.122 AC: 425 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.2
DANN	Benign	0.58
PhyloP100		0.43
Mutation Taster		=99/1	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: rs10519195; hg19: chr15-49163184;