ENST00000473559.5:c.-74+14780C>T

Variant names:

• chr4-86911448-G-A
• rs3113494
• ENST00000473559.5:c.-74+14780C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000473559.5(C4orf36):​c.-74+14780C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,080 control chromosomes in the GnomAD database, including 15,250 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 0.41 (15250 hom., cov: 32)
• Consequence: C4orf36 ENST00000473559.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.595
• Publications: 9 publications found

Genes affected

C4orf36 (HGNC:):

C4orf36 (HGNC:28386): (chromosome 4 open reading frame 36)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C4orf36	NM_001414639.1	c.-74+14780C>T		intron_variant	Intron 4 of 6		NP_001401568.1
C4orf36	NM_001414640.1	c.-142-815C>T		intron_variant	Intron 2 of 5		NP_001401569.1
C4orf36	NM_001414641.1	c.-74+14780C>T		intron_variant	Intron 3 of 5		NP_001401570.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C4orf36	ENST00000473559.5	c.-74+14780C>T		intron_variant	Intron 4 of 6	2		ENSP00000420949.1
C4orf36	ENST00000503001.5	n.438+14780C>T		intron_variant	Intron 3 of 4	3

Frequencies

GnomAD3 genomes AF: 0.408 AC: 62027 AN: 151962 Hom.: 15255 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.408 AC: 62029 AN: 152080 Hom.: 15250 Cov.: 32 AF XY: 0.409 AC XY: 30365 AN XY: 74314

African (AFR) AF: 0.121 AC: 5030 AN: 41496

American (AMR) AF: 0.453 AC: 6907 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2151 AN: 3472

East Asian (EAS) AF: 0.347 AC: 1794 AN: 5174

South Asian (SAS) AF: 0.577 AC: 2783 AN: 4826

European-Finnish (FIN) AF: 0.456 AC: 4812 AN: 10554

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.543 AC: 36880 AN: 67978

Other (OTH) AF: 0.450 AC: 951 AN: 2112

Alfa AF: 0.503 Hom.: 89783

Bravo AF: 0.393

Asia WGS AF: 0.503 AC: 1750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.074
DANN	Benign	0.34
PhyloP100		-0.59
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: rs3113494; hg19: chr4-87832601;