chr15-48929394-G-T

Variant names:

• chr15-48929394-G-T
• rs10519201
• NM_203349.4:c.586-4445C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_203349.4(SHC4):​c.586-4445C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,218 control chromosomes in the GnomAD database, including 1,611 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 0.13 (1611 hom., cov: 32)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203349.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHC4	NM_203349.4	MANE Select	c.586-4445C>A		intron	N/A	NP_976224.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHC4	ENST00000332408.9	TSL:1 MANE Select	c.586-4445C>A		intron	N/A	ENSP00000329668.4

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19577 AN: 152098 Hom.: 1608 Cov.: 32

Gnomad AFR AF: 0.0442

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.0738

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.129 AC: 19592 AN: 152218 Hom.: 1611 Cov.: 32 AF XY: 0.135 AC XY: 10082 AN XY: 74410

African (AFR) AF: 0.0442 AC: 1837 AN: 41572

American (AMR) AF: 0.225 AC: 3443 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0738 AC: 256 AN: 3470

East Asian (EAS) AF: 0.228 AC: 1182 AN: 5176

South Asian (SAS) AF: 0.261 AC: 1259 AN: 4820

European-Finnish (FIN) AF: 0.189 AC: 2001 AN: 10582

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9294 AN: 67994

Other (OTH) AF: 0.121 AC: 255 AN: 2112

Alfa AF: 0.129 Hom.: 2999

Bravo AF: 0.127

Asia WGS AF: 0.290 AC: 1008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.8
DANN	Benign	0.52
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10519201; hg19: chr15-49221591;