rs16961946

Positions:

• chr15-48961696-G-A
• chr15-48961696-G-C

Variant summary

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

The NM_203349.4(SHC4):​c.585+735C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,090 control chromosomes in the GnomAD database, including 2,041 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 (2041 hom., cov: 33)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.662

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 (EAS) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHC4	NM_203349.4	c.585+735C>T		intron_variant		ENST00000332408.9	NP_976224.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHC4	ENST00000332408.9	c.585+735C>T		intron_variant		1	NM_203349.4	ENSP00000329668.4

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20331 AN: 151972 Hom.: 2040 Cov.: 33

Gnomad AFR AF: 0.0299

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.134 AC: 20334 AN: 152090 Hom.: 2041 Cov.: 33 AF XY: 0.140 AC XY: 10381 AN XY: 74332

Gnomad4 AFR AF: 0.0298

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.491

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.113

Alfa AF: 0.140 Hom.: 1379

Bravo AF: 0.125

Asia WGS AF: 0.223 AC: 775 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	0.61
DANN	Benign	0.39

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: rs16961946; hg19: chr15-49253893;