ENST00000473559.5:c.-74+1249G>A

Variant names:

• chr4-86924979-C-T
• rs2785
• ENST00000473559.5:c.-74+1249G>A

Variant summary

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

The ENST00000473559.5(C4orf36):​c.-74+1249G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 152,016 control chromosomes in the GnomAD database, including 15,371 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 (15368 hom., cov: 32)
  • Exomes 𝑓: 0.54 (3 hom.)
• Consequence: C4orf36 ENST00000473559.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 6 publications found

Genes affected

C4orf36 (HGNC:):

AFF1-AS1 (HGNC:53447): (AFF1 antisense RNA 1)

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000473559.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFF1-AS1	NR_038841.1		n.1860G>A		non_coding_transcript_exon	Exon 3 of 3
	C4orf36	NM_001414639.1		c.-74+1249G>A		intron	N/A	NP_001401568.1
	C4orf36	NM_001414640.1		c.-143+1249G>A		intron	N/A	NP_001401569.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C4orf36	ENST00000473559.5	TSL:2	c.-74+1249G>A		intron	N/A	ENSP00000420949.1
	ENSG00000284968	ENST00000508280.6	TSL:2	n.1809G>A		non_coding_transcript_exon	Exon 4 of 4
	C4orf36	ENST00000503001.5	TSL:3	n.438+1249G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62224 AN: 151874 Hom.: 15370 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.453

GnomAD4 exome AF: 0.542 AC: 13 AN: 24 Hom.: 3 Cov.: 0 AF XY: 0.500 AC XY: 9 AN XY: 18

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.542 AC: 13 AN: 24

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.409 AC: 62227 AN: 151992 Hom.: 15368 Cov.: 32 AF XY: 0.410 AC XY: 30448 AN XY: 74290

African (AFR) AF: 0.122 AC: 5061 AN: 41482

American (AMR) AF: 0.454 AC: 6925 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2241 AN: 3472

East Asian (EAS) AF: 0.350 AC: 1806 AN: 5158

South Asian (SAS) AF: 0.578 AC: 2778 AN: 4810

European-Finnish (FIN) AF: 0.456 AC: 4813 AN: 10544

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.543 AC: 36926 AN: 67956

Other (OTH) AF: 0.453 AC: 953 AN: 2102

Alfa AF: 0.333 Hom.: 1023

Bravo AF: 0.395

Asia WGS AF: 0.502 AC: 1746 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	3.3
DANN	Benign	0.68
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: rs2785; hg19: chr4-87846131;