15-48914705-A-G

Variant names:

• chr15-48914705-A-G
• rs934741
• NM_203349.4:c.656+10174T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_203349.4(SHC4):​c.656+10174T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 152,094 control chromosomes in the GnomAD database, including 32,121 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 0.64 (32121 hom., cov: 33)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.542
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHC4	NM_203349.4	c.656+10174T>C		intron_variant	Intron 2 of 11	ENST00000332408.9	NP_976224.3
SHC4	XM_005254375.4	c.107+10174T>C		intron_variant	Intron 2 of 11		XP_005254432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHC4	ENST00000332408.9	c.656+10174T>C		intron_variant	Intron 2 of 11	1	NM_203349.4	ENSP00000329668.4

Frequencies

GnomAD3 genomes AF: 0.639 AC: 97067 AN: 151976 Hom.: 32103 Cov.: 33

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.760

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.639 AC: 97124 AN: 152094 Hom.: 32121 Cov.: 33 AF XY: 0.644 AC XY: 47864 AN XY: 74356

African (AFR) AF: 0.446 AC: 18509 AN: 41472

American (AMR) AF: 0.735 AC: 11236 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.760 AC: 2638 AN: 3470

East Asian (EAS) AF: 0.706 AC: 3657 AN: 5180

South Asian (SAS) AF: 0.780 AC: 3762 AN: 4822

European-Finnish (FIN) AF: 0.709 AC: 7489 AN: 10558

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.699 AC: 47503 AN: 67994

Other (OTH) AF: 0.671 AC: 1415 AN: 2110

Alfa AF: 0.683 Hom.: 65919

Bravo AF: 0.632

Asia WGS AF: 0.698 AC: 2426 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.71
PhyloP100		0.54
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: rs934741; hg19: chr15-49206902;