rs7164451

chr15-48921859-G-A

Variant summary

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

The NM_203349.4(SHC4):c.656+3020C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 152,058 control chromosomes in the GnomAD database, including 31,365 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 0.64 (31365 hom., cov: 32)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.575

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHC4	NM_203349.4	c.656+3020C>T		intron_variant		ENST00000332408.9
SHC4	XM_005254375.4	c.107+3020C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHC4	ENST00000332408.9	c.656+3020C>T		intron_variant		1	NM_203349.4	P1

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97232 AN: 151940 Hom.: 31345 Cov.: 32

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.640 AC: 97309 AN: 152058 Hom.: 31365 Cov.: 32 AF XY: 0.645 AC XY: 47939 AN XY: 74330

Gnomad4 AFR AF: 0.599

Gnomad4 AMR AF: 0.702

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.714

Gnomad4 SAS AF: 0.654

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.620

Alfa AF: 0.632 Hom.: 28228

Bravo AF: 0.637

Asia WGS AF: 0.674 AC: 2344 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.63
Dann	Benign	0.37

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: rs7164451; hg19: chr15-49214056;