rs4443878

Variant names:

• chr1-240741118-C-T
• rs4443878
• ENST00000431139.4:n.315-1265G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000431139.4(ENSG00000230015):​n.315-1265G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 152,230 control chromosomes in the GnomAD database, including 42 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 0.020 (42 hom., cov: 33)
• Consequence: ENSG00000230015 ENST00000431139.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.315
• Publications: 0 publications found

Genes affected

ENSG00000230015 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0198 (3014/152230) while in subpopulation NFE AF = 0.028 (1905/68008). AF 95% confidence interval is 0.027. There are 42 homozygotes in GnomAd4. There are 1437 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 42 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100506929	NR_188400.1	n.61-1265G>A		intron_variant	Intron 1 of 1
LOC100506929	NR_188401.1	n.386-1265G>A		intron_variant	Intron 2 of 2
LOC100506929	NR_188402.1	n.169-1265G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000230015	ENST00000431139.4	n.315-1265G>A		intron_variant	Intron 1 of 1	6
ENSG00000230015	ENST00000688796.1	n.540-1265G>A		intron_variant	Intron 2 of 2
ENSG00000230015	ENST00000817149.1	n.49-1265G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0198 AC: 3011 AN: 152112 Hom.: 42 Cov.: 33

Gnomad AFR AF: 0.0105

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0186

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0161

Gnomad FIN AF: 0.0181

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0280

Gnomad OTH AF: 0.0172

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

GnomAD4 genome AF: 0.0198 AC: 3014 AN: 152230 Hom.: 42 Cov.: 33 AF XY: 0.0193 AC XY: 1437 AN XY: 74444

African (AFR) AF: 0.0105 AC: 437 AN: 41542

American (AMR) AF: 0.0185 AC: 283 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 61 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.0164 AC: 79 AN: 4830

European-Finnish (FIN) AF: 0.0181 AC: 191 AN: 10578

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0280 AC: 1905 AN: 68008

Other (OTH) AF: 0.0189 AC: 40 AN: 2114

Alfa AF: 0.0236 Hom.: 36

Bravo AF: 0.0186

Asia WGS AF: 0.00924 AC: 33 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.4
DANN	Benign	0.83
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4443878; hg19: chr1-240904418;