NM_203349.4:c.585+735C>T

Variant names:

• chr15-48961696-G-A
• rs16961946
• NM_203349.4:c.585+735C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SHC4	NM_203349.4	c.585+735C>T		intron_variant	Intron 1 of 11	ENST00000332408.9	NP_976224.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHC4	ENST00000332408.9	c.585+735C>T		intron_variant	Intron 1 of 11	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

African (AFR) AF: 0.0298 AC: 1238 AN: 41492

American (AMR) AF: 0.129 AC: 1967 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 385 AN: 3470

East Asian (EAS) AF: 0.491 AC: 2538 AN: 5174

South Asian (SAS) AF: 0.119 AC: 575 AN: 4820

European-Finnish (FIN) AF: 0.229 AC: 2416 AN: 10538

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10809 AN: 67988

Other (OTH) AF: 0.113 AC: 239 AN: 2112

Alfa AF: 0.137 Hom.: 1763

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
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16961946; hg19: chr15-49253893;