rs9806753

Variant names:

• chr15-48874220-A-G
• rs9806753
• NM_203349.4:c.841-2078T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-48874220-A-G
• chr15-48874220-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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=-0.97).
• 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 rank	MANE	Protein	UniProt
SHC4	NM_203349.4	c.841-2078T>C		intron_variant	Intron 4 of 11	ENST00000332408.9	NP_976224.3
SHC4	XM_005254375.4	c.292-2078T>C		intron_variant	Intron 4 of 11		XP_005254432.1
SHC4	XM_047432492.1	c.-18-2078T>C		intron_variant	Intron 1 of 8		XP_047288448.1
SHC4	XM_047432493.1	c.-18-2078T>C		intron_variant	Intron 2 of 9		XP_047288449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHC4	ENST00000332408.9	c.841-2078T>C		intron_variant	Intron 4 of 11	1	NM_203349.4	ENSP00000329668.4

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

African (AFR) AF: 0.499 AC: 20652 AN: 41410

American (AMR) AF: 0.646 AC: 9861 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 2861 AN: 3472

East Asian (EAS) AF: 0.720 AC: 3727 AN: 5176

South Asian (SAS) AF: 0.689 AC: 3314 AN: 4812

European-Finnish (FIN) AF: 0.641 AC: 6766 AN: 10554

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.742 AC: 50475 AN: 67986

Other (OTH) AF: 0.701 AC: 1478 AN: 2108

Alfa AF: 0.725 Hom.: 23149

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
PhyloP100		0.44
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: rs9806753; hg19: chr15-49166417;