rs4775783

Positions:

• chr15-48884006-A-T

Variant summary

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

The NM_203349.4(SHC4):​c.840+242T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,044 control chromosomes in the GnomAD database, including 5,855 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 0.25 (5855 hom., cov: 32)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.173

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHC4	NM_203349.4	c.840+242T>A		intron_variant		ENST00000332408.9
SHC4	XM_005254375.4	c.291+242T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHC4	ENST00000332408.9	c.840+242T>A		intron_variant		1	NM_203349.4	P1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37451 AN: 151926 Hom.: 5827 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.0965

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.247 AC: 37529 AN: 152044 Hom.: 5855 Cov.: 32 AF XY: 0.258 AC XY: 19142 AN XY: 74298

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.0965

Gnomad4 EAS AF: 0.559

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.212

Alfa AF: 0.198 Hom.: 472

Bravo AF: 0.258

Asia WGS AF: 0.467 AC: 1619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.6
DANN	Benign	0.73

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: rs4775783; hg19: chr15-49176203;