15-48927578-T-G

Variant names:

• chr15-48927578-T-G
• rs10519199
• NM_203349.4:c.586-2629A>C

Variant summary

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

The NM_203349.4(SHC4):​c.586-2629A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 151,844 control chromosomes in the GnomAD database, including 8,504 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 0.32 (8504 hom., cov: 31)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHC4	NM_203349.4	c.586-2629A>C		intron_variant	Intron 1 of 11	ENST00000332408.9	NP_976224.3
SHC4	XM_005254375.4	c.37-2629A>C		intron_variant	Intron 1 of 11		XP_005254432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHC4	ENST00000332408.9	c.586-2629A>C		intron_variant	Intron 1 of 11	1	NM_203349.4	ENSP00000329668.4

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49282 AN: 151726 Hom.: 8490 Cov.: 31

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.325 AC: 49343 AN: 151844 Hom.: 8504 Cov.: 31 AF XY: 0.327 AC XY: 24234 AN XY: 74208

African (AFR) AF: 0.401 AC: 16607 AN: 41368

American (AMR) AF: 0.380 AC: 5796 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 753 AN: 3464

East Asian (EAS) AF: 0.529 AC: 2728 AN: 5154

South Asian (SAS) AF: 0.384 AC: 1847 AN: 4810

European-Finnish (FIN) AF: 0.271 AC: 2857 AN: 10536

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17956 AN: 67926

Other (OTH) AF: 0.299 AC: 631 AN: 2112

Alfa AF: 0.278 Hom.: 25719

Bravo AF: 0.337

Asia WGS AF: 0.471 AC: 1636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.41
DANN	Benign	0.48
PhyloP100		-0.0050
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs10519199; hg19: chr15-49219775;