15-48846757-A-T

Position:

• chr15-48846757-A-T

Variant summary

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

The NM_203349.4(SHC4):​c.1304-3169T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0421 in 152,258 control chromosomes in the GnomAD database, including 277 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 0.042 (277 hom., cov: 32)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.427

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHC4	NM_203349.4	c.1304-3169T>A		intron_variant		ENST00000332408.9	NP_976224.3
SHC4	XM_005254375.4	c.755-3169T>A		intron_variant			XP_005254432.1
SHC4	XM_047432492.1	c.446-3169T>A		intron_variant			XP_047288448.1
SHC4	XM_047432493.1	c.446-3169T>A		intron_variant			XP_047288449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHC4	ENST00000332408.9	c.1304-3169T>A		intron_variant		1	NM_203349.4	ENSP00000329668.4
SHC4	ENST00000396535.7	c.575-3169T>A		intron_variant		1		ENSP00000379786.3
SHC4	ENST00000537958.5	c.446-3169T>A		intron_variant		2		ENSP00000443300.1
SHC4	ENST00000557797.5	n.385-3169T>A		intron_variant		3		ENSP00000453344.1

Frequencies

GnomAD3 genomes AF: 0.0421 AC: 6399 AN: 152140 Hom.: 277 Cov.: 32

Gnomad AFR AF: 0.0525

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0384

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.0336

Gnomad FIN AF: 0.0700

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0212

Gnomad OTH AF: 0.0402

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

GnomAD4 genome AF: 0.0421 AC: 6406 AN: 152258 Hom.: 277 Cov.: 32 AF XY: 0.0439 AC XY: 3265 AN XY: 74448

Gnomad4 AFR AF: 0.0525

Gnomad4 AMR AF: 0.0386

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.0334

Gnomad4 FIN AF: 0.0700

Gnomad4 NFE AF: 0.0212

Gnomad4 OTH AF: 0.0416

Alfa AF: 0.00804 Hom.: 5

Bravo AF: 0.0418

Asia WGS AF: 0.118 AC: 409 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.49

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: rs8036806; hg19: chr15-49138954;