15-48929394-G-T

Position:

• chr15-48929394-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.586-4445C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,218 control chromosomes in the GnomAD database, including 1,611 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 0.13 (1611 hom., cov: 32)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHC4	NM_203349.4	c.586-4445C>A		intron_variant		ENST00000332408.9	NP_976224.3
SHC4	XM_005254375.4	c.37-4445C>A		intron_variant			XP_005254432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHC4	ENST00000332408.9	c.586-4445C>A		intron_variant		1	NM_203349.4	ENSP00000329668.4

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19577 AN: 152098 Hom.: 1608 Cov.: 32

Gnomad AFR AF: 0.0442

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.0738

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.129 AC: 19592 AN: 152218 Hom.: 1611 Cov.: 32 AF XY: 0.135 AC XY: 10082 AN XY: 74410

Gnomad4 AFR AF: 0.0442

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.0738

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.121

Alfa AF: 0.132 Hom.: 1839

Bravo AF: 0.127

Asia WGS AF: 0.290 AC: 1008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.8
DANN	Benign	0.52

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: rs10519201; hg19: chr15-49221591;