chr15-48874220-A-G

Position:

• chr15-48874220-A-G

Variant summary

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

The NM_203349.4(SHC4):​c.841-2078T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 151,988 control chromosomes in the GnomAD database, including 33,931 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 0.66 (33931 hom., cov: 32)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.442

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHC4	NM_203349.4	c.841-2078T>C		intron_variant		ENST00000332408.9
SHC4	XM_005254375.4	c.292-2078T>C		intron_variant
SHC4	XM_047432492.1	c.-18-2078T>C		intron_variant
SHC4	XM_047432493.1	c.-18-2078T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHC4	ENST00000332408.9	c.841-2078T>C		intron_variant		1	NM_203349.4	P1

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100069 AN: 151870 Hom.: 33925 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.742

Gnomad OTH AF: 0.706

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

GnomAD4 genome AF: 0.659 AC: 100120 AN: 151988 Hom.: 33931 Cov.: 32 AF XY: 0.653 AC XY: 48506 AN XY: 74262

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.646

Gnomad4 ASJ AF: 0.824

Gnomad4 EAS AF: 0.720

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.641

Gnomad4 NFE AF: 0.742

Gnomad4 OTH AF: 0.701

Alfa AF: 0.725 Hom.: 20931

Bravo AF: 0.651

Asia WGS AF: 0.660 AC: 2296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	6.9
DANN	Benign	0.60

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: rs9806753; hg19: chr15-49166417;