rs2413922

Variant names:

• chr15-48929684-G-A
• rs2413922
• NM_203349.4:c.586-4735C>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.586-4735C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,150 control chromosomes in the GnomAD database, including 10,733 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 0.37 (10733 hom., cov: 32)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384
• 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 (NFE) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203349.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHC4	NM_203349.4	MANE Select	c.586-4735C>T		intron	N/A	NP_976224.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHC4	ENST00000332408.9	TSL:1 MANE Select	c.586-4735C>T		intron	N/A	ENSP00000329668.4

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55584 AN: 152032 Hom.: 10732 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.0948

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.365 AC: 55601 AN: 152150 Hom.: 10733 Cov.: 32 AF XY: 0.357 AC XY: 26576 AN XY: 74390

African (AFR) AF: 0.376 AC: 15598 AN: 41498

American (AMR) AF: 0.343 AC: 5250 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1833 AN: 3472

East Asian (EAS) AF: 0.0946 AC: 490 AN: 5180

South Asian (SAS) AF: 0.341 AC: 1645 AN: 4822

European-Finnish (FIN) AF: 0.230 AC: 2432 AN: 10590

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26774 AN: 67982

Other (OTH) AF: 0.420 AC: 887 AN: 2114

Alfa AF: 0.390 Hom.: 10714

Bravo AF: 0.372

Asia WGS AF: 0.202 AC: 705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.70
PhyloP100		-0.38
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: rs2413922; hg19: chr15-49221881;