rs17384124

Variant names:

• chr15-48926310-G-A
• rs17384124
• NM_203349.4:c.586-1361C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-48926310-G-A
• chr15-48926310-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.586-1361C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,100 control chromosomes in the GnomAD database, including 992 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 0.11 (992 hom., cov: 31)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28
• Publications: 7 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHC4	NM_203349.4	c.586-1361C>T		intron_variant	Intron 1 of 11	ENST00000332408.9	NP_976224.3
SHC4	XM_005254375.4	c.37-1361C>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.586-1361C>T		intron_variant	Intron 1 of 11	1	NM_203349.4	ENSP00000329668.4

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16457 AN: 151982 Hom.: 990 Cov.: 31

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0489

Gnomad FIN AF: 0.0468

Gnomad MID AF: 0.166

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.108 AC: 16476 AN: 152100 Hom.: 992 Cov.: 31 AF XY: 0.104 AC XY: 7741 AN XY: 74390

African (AFR) AF: 0.133 AC: 5503 AN: 41462

American (AMR) AF: 0.114 AC: 1745 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 427 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5178

South Asian (SAS) AF: 0.0492 AC: 237 AN: 4818

European-Finnish (FIN) AF: 0.0468 AC: 497 AN: 10614

Middle Eastern (MID) AF: 0.161 AC: 47 AN: 292

European-Non Finnish (NFE) AF: 0.112 AC: 7624 AN: 67980

Other (OTH) AF: 0.131 AC: 277 AN: 2110

Alfa AF: 0.111 Hom.: 2008

Bravo AF: 0.114

Asia WGS AF: 0.0310 AC: 107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0090
DANN	Benign	0.56
PhyloP100		-2.3
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: rs17384124; hg19: chr15-49218507;