rs17382306

Positions:

• chr15-48843829-G-A
• chr15-48843829-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.1304-241C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 151,972 control chromosomes in the GnomAD database, including 2,374 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 0.17 (2374 hom., cov: 32)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.144

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHC4	NM_203349.4	c.1304-241C>T		intron_variant		ENST00000332408.9
SHC4	XM_005254375.4	c.755-241C>T		intron_variant
SHC4	XM_047432492.1	c.446-241C>T		intron_variant
SHC4	XM_047432493.1	c.446-241C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHC4	ENST00000332408.9	c.1304-241C>T		intron_variant		1	NM_203349.4	P1
SHC4	ENST00000396535.7	c.575-241C>T		intron_variant		1
SHC4	ENST00000537958.5	c.446-241C>T		intron_variant		2
SHC4	ENST00000557797.5	c.385-241C>T		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25484 AN: 151854 Hom.: 2374 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.0803

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.168 AC: 25506 AN: 151972 Hom.: 2374 Cov.: 32 AF XY: 0.166 AC XY: 12303 AN XY: 74242

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.0803

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.159

Alfa AF: 0.196 Hom.: 3080

Bravo AF: 0.158

Asia WGS AF: 0.153 AC: 534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.69

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: rs17382306; hg19: chr15-49136026;