15-48914600-A-G

Position:

• chr15-48914600-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_203349.4(SHC4):​c.656+10279T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 152,086 control chromosomes in the GnomAD database, including 43,033 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 0.72 (43033 hom., cov: 32)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.897

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHC4	NM_203349.4	c.656+10279T>C		intron_variant		ENST00000332408.9	NP_976224.3
SHC4	XM_005254375.4	c.107+10279T>C		intron_variant			XP_005254432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHC4	ENST00000332408.9	c.656+10279T>C		intron_variant		1	NM_203349.4	ENSP00000329668.4

Frequencies

GnomAD3 genomes AF: 0.724 AC: 110030 AN: 151968 Hom.: 43023 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.924

Gnomad AMR AF: 0.836

Gnomad ASJ AF: 0.852

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.862

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.847

Gnomad OTH AF: 0.769

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

GnomAD4 genome AF: 0.724 AC: 110070 AN: 152086 Hom.: 43033 Cov.: 32 AF XY: 0.731 AC XY: 54371 AN XY: 74334

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.835

Gnomad4 ASJ AF: 0.852

Gnomad4 EAS AF: 0.803

Gnomad4 SAS AF: 0.863

Gnomad4 FIN AF: 0.887

Gnomad4 NFE AF: 0.847

Gnomad4 OTH AF: 0.771

Alfa AF: 0.817 Hom.: 43945

Bravo AF: 0.707

Asia WGS AF: 0.768 AC: 2673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.43
DANN	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs934740; hg19: chr15-49206797;