15-48961280-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.585+1151T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 152,114 control chromosomes in the GnomAD database, including 9,801 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 0.35 (9801 hom., cov: 32)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.454

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHC4	NM_203349.4	c.585+1151T>C		intron_variant		ENST00000332408.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHC4	ENST00000332408.9	c.585+1151T>C		intron_variant		1	NM_203349.4	P1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53629 AN: 151996 Hom.: 9803 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.0812

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.353 AC: 53636 AN: 152114 Hom.: 9801 Cov.: 32 AF XY: 0.350 AC XY: 25993 AN XY: 74366

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.0814

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.342

Alfa AF: 0.365 Hom.: 14824

Bravo AF: 0.343

Asia WGS AF: 0.235 AC: 815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	3.7
Dann	Benign	0.58

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: rs11636875; hg19: chr15-49253477;