rs10519193

Positions:

• chr15-48870756-T-C
• chr15-48870756-T-G

Variant summary

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

The NM_203349.4(SHC4):​c.894+1333A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 152,080 control chromosomes in the GnomAD database, including 28,893 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 0.59 (28893 hom., cov: 32)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHC4	NM_203349.4	c.894+1333A>G		intron_variant		ENST00000332408.9	NP_976224.3
SHC4	XM_005254375.4	c.345+1333A>G		intron_variant			XP_005254432.1
SHC4	XM_047432492.1	c.36+1333A>G		intron_variant			XP_047288448.1
SHC4	XM_047432493.1	c.36+1333A>G		intron_variant			XP_047288449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHC4	ENST00000332408.9	c.894+1333A>G		intron_variant		1	NM_203349.4	ENSP00000329668	P1

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90407 AN: 151964 Hom.: 28891 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.722

Gnomad OTH AF: 0.654

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

GnomAD4 genome AF: 0.595 AC: 90432 AN: 152080 Hom.: 28893 Cov.: 32 AF XY: 0.588 AC XY: 43733 AN XY: 74330

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.602

Gnomad4 ASJ AF: 0.827

Gnomad4 EAS AF: 0.496

Gnomad4 SAS AF: 0.665

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.722

Gnomad4 OTH AF: 0.648

Alfa AF: 0.709 Hom.: 62157

Bravo AF: 0.585

Asia WGS AF: 0.535 AC: 1864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.3
DANN	Benign	0.78

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: rs10519193; hg19: chr15-49162953;