rs4259993

Variant names:

• chr15-48932175-G-A
• rs4259993
• NM_203349.4:c.586-7226C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-48932175-G-A
• chr15-48932175-G-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.586-7226C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 151,800 control chromosomes in the GnomAD database, including 2,516 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 0.18 (2516 hom., cov: 31)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.488
• Publications: 1 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHC4	NM_203349.4	c.586-7226C>T		intron_variant	Intron 1 of 11	ENST00000332408.9	NP_976224.3
SHC4	XM_005254375.4	c.37-7226C>T		intron_variant	Intron 1 of 11		XP_005254432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHC4	ENST00000332408.9	c.586-7226C>T		intron_variant	Intron 1 of 11	1	NM_203349.4	ENSP00000329668.4

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26722 AN: 151682 Hom.: 2516 Cov.: 31

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.176 AC: 26739 AN: 151800 Hom.: 2516 Cov.: 31 AF XY: 0.180 AC XY: 13363 AN XY: 74172

African (AFR) AF: 0.126 AC: 5219 AN: 41384

American (AMR) AF: 0.143 AC: 2181 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 603 AN: 3468

East Asian (EAS) AF: 0.313 AC: 1604 AN: 5124

South Asian (SAS) AF: 0.161 AC: 775 AN: 4800

European-Finnish (FIN) AF: 0.285 AC: 2998 AN: 10528

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.189 AC: 12826 AN: 67912

Other (OTH) AF: 0.170 AC: 359 AN: 2112

Alfa AF: 0.178 Hom.: 2428

Bravo AF: 0.163

Asia WGS AF: 0.248 AC: 860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.62
DANN	Benign	0.51
PhyloP100		-0.49
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: rs4259993; hg19: chr15-49224372;