chr15-48859206-C-T

Variant names:

• chr15-48859206-C-T
• rs1974961
• NM_203349.4:c.947-1391G>A

Variant summary

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

The NM_203349.4(SHC4):​c.947-1391G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 152,150 control chromosomes in the GnomAD database, including 53,404 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 0.83 (53404 hom., cov: 31)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHC4	NM_203349.4	c.947-1391G>A		intron_variant	Intron 6 of 11	ENST00000332408.9	NP_976224.3
SHC4	XM_005254375.4	c.398-1391G>A		intron_variant	Intron 6 of 11		XP_005254432.1
SHC4	XM_047432492.1	c.89-1391G>A		intron_variant	Intron 3 of 8		XP_047288448.1
SHC4	XM_047432493.1	c.89-1391G>A		intron_variant	Intron 4 of 9		XP_047288449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHC4	ENST00000332408.9	c.947-1391G>A		intron_variant	Intron 6 of 11	1	NM_203349.4	ENSP00000329668.4

Frequencies

GnomAD3 genomes AF: 0.835 AC: 126873 AN: 152032 Hom.: 53359 Cov.: 31

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.903

Gnomad ASJ AF: 0.902

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.908

Gnomad FIN AF: 0.862

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.859

Gnomad OTH AF: 0.851

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

GnomAD4 genome AF: 0.835 AC: 126977 AN: 152150 Hom.: 53404 Cov.: 31 AF XY: 0.839 AC XY: 62388 AN XY: 74402

Gnomad4 AFR AF: 0.725

Gnomad4 AMR AF: 0.903

Gnomad4 ASJ AF: 0.902

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.907

Gnomad4 FIN AF: 0.862

Gnomad4 NFE AF: 0.859

Gnomad4 OTH AF: 0.852

Alfa AF: 0.860 Hom.: 52864

Bravo AF: 0.833

Asia WGS AF: 0.944 AC: 3277 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.22
DANN	Benign	0.64

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: rs1974961; hg19: chr15-49151403; COSMIC: COSV60117804;