15-48946233-C-T

Variant names:

• chr15-48946233-C-T
• rs12898878
• NM_203349.4:c.585+16198G>A

Variant summary

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

The NM_203349.4(SHC4):​c.585+16198G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 152,066 control chromosomes in the GnomAD database, including 15,663 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 0.44 (15663 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.767

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]

ENSG00000259602 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHC4	NM_203349.4	c.585+16198G>A		intron_variant	Intron 1 of 11	ENST00000332408.9	NP_976224.3
SHC4	XM_005254375.4	c.36+327G>A		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.585+16198G>A		intron_variant	Intron 1 of 11	1	NM_203349.4	ENSP00000329668.4
ENSG00000259602	ENST00000559620.1	n.316+103C>T		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67620 AN: 151948 Hom.: 15658 Cov.: 33

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.713

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.504

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.445 AC: 67660 AN: 152066 Hom.: 15663 Cov.: 33 AF XY: 0.442 AC XY: 32826 AN XY: 74326

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.610

Gnomad4 EAS AF: 0.509

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.507

Gnomad4 OTH AF: 0.501

Alfa AF: 0.499 Hom.: 16098

Bravo AF: 0.445

Asia WGS AF: 0.441 AC: 1535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Benign	0.69

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: rs12898878; hg19: chr15-49238430;