chr15-48825352-A-G

Position:

• chr15-48825352-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.*619T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 152,064 control chromosomes in the GnomAD database, including 11,420 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 0.37 (11409 hom., cov: 31)
  • Exomes 𝑓: 0.42 (11 hom.)
• Consequence: SHC4 NM_203349.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.707

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 = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHC4	NM_203349.4	c.*619T>C		3_prime_UTR_variant	12/12	ENST00000332408.9
SHC4	XM_005254375.4	c.*619T>C		3_prime_UTR_variant	12/12
SHC4	XM_047432492.1	c.*619T>C		3_prime_UTR_variant	9/9
SHC4	XM_047432493.1	c.*619T>C		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHC4	ENST00000332408.9	c.*619T>C		3_prime_UTR_variant	12/12	1	NM_203349.4	P1
SHC4	ENST00000396535.7	c.*619T>C		3_prime_UTR_variant	9/9	1

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56698 AN: 151854 Hom.: 11408 Cov.: 31

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.428

GnomAD4 exome AF: 0.424 AC: 39 AN: 92 Hom.: 11 Cov.: 0 AF XY: 0.400 AC XY: 24 AN XY: 60

Gnomad4 AMR exome AF: 0.167

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.458

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.373 AC: 56709 AN: 151972 Hom.: 11409 Cov.: 31 AF XY: 0.367 AC XY: 27222 AN XY: 74236

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.555

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.424

Alfa AF: 0.419 Hom.: 10621

Bravo AF: 0.375

Asia WGS AF: 0.280 AC: 978 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	4.2
DANN	Benign	0.75

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: rs1062124; hg19: chr15-49117549;