chr15-48870756-T-C

Variant names:

• chr15-48870756-T-C
• rs10519193
• NM_203349.4:c.894+1333A>G

Variant summary

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

The NM_203349.4(SHC4):​c.894+1333A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 152,080 control chromosomes in the GnomAD database, including 28,893 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 0.59 (28893 hom., cov: 32)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241
• Publications: 11 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.717 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHC4	NM_203349.4	MANE Select	c.894+1333A>G		intron	N/A	NP_976224.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHC4	ENST00000332408.9	TSL:1 MANE Select	c.894+1333A>G		intron	N/A	ENSP00000329668.4	Q6S5L8-1
	SHC4	ENST00000396535.7	TSL:1	c.165+1333A>G		intron	N/A	ENSP00000379786.3	Q6S5L8-2
	SHC4	ENST00000537958.5	TSL:2	c.36+1333A>G		intron	N/A	ENSP00000443300.1	F5H5M1

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90407 AN: 151964 Hom.: 28891 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.722

Gnomad OTH AF: 0.654

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

GnomAD4 genome AF: 0.595 AC: 90432 AN: 152080 Hom.: 28893 Cov.: 32 AF XY: 0.588 AC XY: 43733 AN XY: 74330

African (AFR) AF: 0.365 AC: 15128 AN: 41484

American (AMR) AF: 0.602 AC: 9200 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.827 AC: 2871 AN: 3470

East Asian (EAS) AF: 0.496 AC: 2561 AN: 5164

South Asian (SAS) AF: 0.665 AC: 3205 AN: 4822

European-Finnish (FIN) AF: 0.570 AC: 6016 AN: 10552

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.722 AC: 49100 AN: 67984

Other (OTH) AF: 0.648 AC: 1372 AN: 2116

Alfa AF: 0.677 Hom.: 96010

Bravo AF: 0.585

Asia WGS AF: 0.535 AC: 1864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.3
DANN	Benign	0.78
PhyloP100		0.24
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: rs10519193; hg19: chr15-49162953;