chr15-48900129-T-C

Position:

• chr15-48900129-T-C

Variant summary

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

The NM_203349.4(SHC4):​c.657-9318A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,096 control chromosomes in the GnomAD database, including 5,035 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 0.23 (5035 hom., cov: 31)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.64

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHC4	NM_203349.4	c.657-9318A>G		intron_variant		ENST00000332408.9	NP_976224.3
SHC4	XM_005254375.4	c.108-9318A>G		intron_variant			XP_005254432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHC4	ENST00000332408.9	c.657-9318A>G		intron_variant		1	NM_203349.4	ENSP00000329668	P1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35156 AN: 151978 Hom.: 5009 Cov.: 31

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.0966

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.232 AC: 35228 AN: 152096 Hom.: 5035 Cov.: 31 AF XY: 0.243 AC XY: 18087 AN XY: 74360

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.0966

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.200

Alfa AF: 0.166 Hom.: 4175

Bravo AF: 0.241

Asia WGS AF: 0.465 AC: 1614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.051
DANN	Benign	0.59

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: rs4775785; hg19: chr15-49192326;