4-23343831-T-G

Variant names:

• chr4-23343831-T-G
• rs1396669
• ENST00000757640.1:n.285-14388A>C

Variant summary

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

The ENST00000757640.1(ENSG00000298732):​n.285-14388A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 151,910 control chromosomes in the GnomAD database, including 11,075 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 (11075 hom., cov: 33)
• Consequence: ENSG00000298732 ENST00000757640.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.523
• Publications: 4 publications found

Genes affected

ENSG00000298732 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105374523	XR_001741614.1	n.227-14388A>C		intron_variant	Intron 1 of 2
LOC105374524	XR_007058437.1	n.2932+10305T>G		intron_variant	Intron 16 of 18
LOC105374523	XR_925460.2	n.227-14388A>C		intron_variant	Intron 1 of 2
LOC105374523	XR_925461.2	n.266-14388A>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000298732	ENST00000757640.1	n.285-14388A>C		intron_variant	Intron 1 of 4
ENSG00000298732	ENST00000757641.1	n.268-14388A>C		intron_variant	Intron 1 of 3
ENSG00000298732	ENST00000757642.1	n.253-14388A>C		intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54427 AN: 151792 Hom.: 11071 Cov.: 33

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.358 AC: 54441 AN: 151910 Hom.: 11075 Cov.: 33 AF XY: 0.361 AC XY: 26761 AN XY: 74220

African (AFR) AF: 0.147 AC: 6106 AN: 41490

American (AMR) AF: 0.446 AC: 6793 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1703 AN: 3468

East Asian (EAS) AF: 0.465 AC: 2382 AN: 5124

South Asian (SAS) AF: 0.424 AC: 2046 AN: 4822

European-Finnish (FIN) AF: 0.425 AC: 4484 AN: 10560

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.436 AC: 29594 AN: 67886

Other (OTH) AF: 0.375 AC: 792 AN: 2112

Alfa AF: 0.408 Hom.: 36308

Bravo AF: 0.350

Asia WGS AF: 0.434 AC: 1508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	10
DANN	Benign	0.57
PhyloP100		0.52

Splicing

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

Other links and lift over

dbSNP: rs1396669; hg19: chr4-23345454;