rs4775777

Variant names:

• chr15-48839414-A-G
• rs4775777
• NM_203349.4:c.1483+3995T>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.1483+3995T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 152,056 control chromosomes in the GnomAD database, including 11,711 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 0.36 (11711 hom., cov: 32)
• Consequence: SHC4 NM_203349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.905
• Publications: 6 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 (NFE) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203349.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHC4	NM_203349.4	MANE Select	c.1483+3995T>C		intron	N/A	NP_976224.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHC4	ENST00000332408.9	TSL:1 MANE Select	c.1483+3995T>C		intron	N/A	ENSP00000329668.4
	SHC4	ENST00000396535.7	TSL:1	c.754+3995T>C		intron	N/A	ENSP00000379786.3
	SHC4	ENST00000537958.5	TSL:2	c.625+3995T>C		intron	N/A	ENSP00000443300.1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55170 AN: 151938 Hom.: 11714 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.363 AC: 55165 AN: 152056 Hom.: 11711 Cov.: 32 AF XY: 0.358 AC XY: 26633 AN XY: 74320

African (AFR) AF: 0.144 AC: 5996 AN: 41498

American (AMR) AF: 0.406 AC: 6204 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1888 AN: 3472

East Asian (EAS) AF: 0.347 AC: 1793 AN: 5170

South Asian (SAS) AF: 0.375 AC: 1806 AN: 4810

European-Finnish (FIN) AF: 0.362 AC: 3827 AN: 10562

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32109 AN: 67934

Other (OTH) AF: 0.422 AC: 893 AN: 2114

Alfa AF: 0.438 Hom.: 8577

Bravo AF: 0.359

Asia WGS AF: 0.289 AC: 1008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.33
DANN	Benign	0.73
PhyloP100		-0.91
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: rs4775777; hg19: chr15-49131611;