rs2413922

Positions:

• chr15-48929684-G-A

Variant summary

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

The NM_203349.4(SHC4):​c.586-4735C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,150 control chromosomes in the GnomAD database, including 10,733 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 0.37 (10733 hom., cov: 32)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHC4	NM_203349.4	c.586-4735C>T		intron_variant		ENST00000332408.9	NP_976224.3
SHC4	XM_005254375.4	c.37-4735C>T		intron_variant			XP_005254432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHC4	ENST00000332408.9	c.586-4735C>T		intron_variant		1	NM_203349.4	ENSP00000329668.4

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55584 AN: 152032 Hom.: 10732 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.0948

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.365 AC: 55601 AN: 152150 Hom.: 10733 Cov.: 32 AF XY: 0.357 AC XY: 26576 AN XY: 74390

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.528

Gnomad4 EAS AF: 0.0946

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.420

Alfa AF: 0.391 Hom.: 7753

Bravo AF: 0.372

Asia WGS AF: 0.202 AC: 705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.70

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: rs2413922; hg19: chr15-49221881;