15-48859810-C-G

Variant names:

• chr15-48859810-C-G
• rs7169897
• NM_203349.4:c.947-1995G>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.947-1995G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,082 control chromosomes in the GnomAD database, including 2,853 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 0.18 (2853 hom., cov: 32)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 4 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 (EAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHC4	NM_203349.4	c.947-1995G>C		intron_variant	Intron 6 of 11	ENST00000332408.9	NP_976224.3
SHC4	XM_005254375.4	c.398-1995G>C		intron_variant	Intron 6 of 11		XP_005254432.1
SHC4	XM_047432492.1	c.89-1995G>C		intron_variant	Intron 3 of 8		XP_047288448.1
SHC4	XM_047432493.1	c.89-1995G>C		intron_variant	Intron 4 of 9		XP_047288449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHC4	ENST00000332408.9	c.947-1995G>C		intron_variant	Intron 6 of 11	1	NM_203349.4	ENSP00000329668.4

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27267 AN: 151964 Hom.: 2842 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.0790

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.180 AC: 27314 AN: 152082 Hom.: 2853 Cov.: 32 AF XY: 0.189 AC XY: 14045 AN XY: 74332

African (AFR) AF: 0.235 AC: 9733 AN: 41466

American (AMR) AF: 0.258 AC: 3941 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0790 AC: 274 AN: 3468

East Asian (EAS) AF: 0.286 AC: 1476 AN: 5162

South Asian (SAS) AF: 0.226 AC: 1092 AN: 4824

European-Finnish (FIN) AF: 0.223 AC: 2351 AN: 10558

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

European-Non Finnish (NFE) AF: 0.118 AC: 7995 AN: 68004

Other (OTH) AF: 0.160 AC: 337 AN: 2110

Alfa AF: 0.0738 Hom.: 93

Bravo AF: 0.186

Asia WGS AF: 0.297 AC: 1032 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	0.10
DANN	Benign	0.51
PhyloP100		-1.0
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: rs7169897; hg19: chr15-49152007;