rs17383671

Variant names:

• chr15-48907180-A-G
• rs17383671
• NM_203349.4:c.657-16369T>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.657-16369T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 151,776 control chromosomes in the GnomAD database, including 1,470 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 0.12 (1470 hom., cov: 31)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHC4	NM_203349.4	c.657-16369T>C		intron_variant	Intron 2 of 11	ENST00000332408.9	NP_976224.3
SHC4	XM_005254375.4	c.108-16369T>C		intron_variant	Intron 2 of 11		XP_005254432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHC4	ENST00000332408.9	c.657-16369T>C		intron_variant	Intron 2 of 11	1	NM_203349.4	ENSP00000329668.4

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18396 AN: 151660 Hom.: 1469 Cov.: 31

Gnomad AFR AF: 0.0338

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0873

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.0853

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.0939

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

GnomAD4 genome AF: 0.121 AC: 18403 AN: 151776 Hom.: 1470 Cov.: 31 AF XY: 0.122 AC XY: 9069 AN XY: 74178

African (AFR) AF: 0.0337 AC: 1394 AN: 41424

American (AMR) AF: 0.0877 AC: 1337 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 347 AN: 3470

East Asian (EAS) AF: 0.0851 AC: 440 AN: 5172

South Asian (SAS) AF: 0.136 AC: 650 AN: 4788

European-Finnish (FIN) AF: 0.224 AC: 2345 AN: 10480

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11558 AN: 67884

Other (OTH) AF: 0.0948 AC: 200 AN: 2110

Alfa AF: 0.138 Hom.: 324

Bravo AF: 0.105

Asia WGS AF: 0.136 AC: 475 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	2.5
DANN	Benign	0.52
PhyloP100		-0.078
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17383671; hg19: chr15-49199377;