rs7162426

Positions:

• chr15-48895477-G-A
• chr15-48895477-G-C

Variant summary

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

The NM_203349.4(SHC4):​c.657-4666C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,014 control chromosomes in the GnomAD database, including 2,251 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 0.16 (2251 hom., cov: 31)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHC4	NM_203349.4	c.657-4666C>T		intron_variant		ENST00000332408.9	NP_976224.3
SHC4	XM_005254375.4	c.108-4666C>T		intron_variant			XP_005254432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHC4	ENST00000332408.9	c.657-4666C>T		intron_variant		1	NM_203349.4	ENSP00000329668	P1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23867 AN: 151896 Hom.: 2241 Cov.: 31

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.157 AC: 23891 AN: 152014 Hom.: 2251 Cov.: 31 AF XY: 0.167 AC XY: 12427 AN XY: 74272

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.0657

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.140

Alfa AF: 0.112 Hom.: 581

Bravo AF: 0.163

Asia WGS AF: 0.303 AC: 1053 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	1.1
DANN	Benign	0.66

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: rs7162426; hg19: chr15-49187674;