chr15-48892484-G-A

Position:

• chr15-48892484-G-A

Variant summary

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

The ENST00000332408.9(SHC4):​c.657-1673C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 151,940 control chromosomes in the GnomAD database, including 6,944 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 0.27 (6944 hom., cov: 31)
• Consequence: SHC4 ENST00000332408.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHC4	NM_203349.4	c.657-1673C>T		intron_variant		ENST00000332408.9	NP_976224.3
SHC4	XM_005254375.4	c.108-1673C>T		intron_variant			XP_005254432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHC4	ENST00000332408.9	c.657-1673C>T		intron_variant		1	NM_203349.4	ENSP00000329668	P1

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40334 AN: 151822 Hom.: 6944 Cov.: 31

Gnomad AFR AF: 0.0757

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.0608

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.265 AC: 40333 AN: 151940 Hom.: 6944 Cov.: 31 AF XY: 0.261 AC XY: 19342 AN XY: 74226

Gnomad4 AFR AF: 0.0755

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.492

Gnomad4 EAS AF: 0.0606

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.328

Alfa AF: 0.361 Hom.: 13875

Bravo AF: 0.259

Asia WGS AF: 0.159 AC: 555 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.45
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: rs4774527; hg19: chr15-49184681;