rs4375593

Positions:

• chr14-94600896-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000553947.1(ENSG00000273259):​n.*667+2685G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 151,570 control chromosomes in the GnomAD database, including 12,407 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 0.39 (12407 hom., cov: 31)
• Consequence: ENSG00000273259 ENST00000553947.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.841

Genes affected

ENSG00000273259 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000273259	ENST00000553947.1	n.*667+2685G>A		intron_variant		2		ENSP00000452367.2
ENSG00000288028	ENST00000656621.1	n.70+1367G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58318 AN: 151452 Hom.: 12381 Cov.: 31

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.385 AC: 58386 AN: 151570 Hom.: 12407 Cov.: 31 AF XY: 0.380 AC XY: 28116 AN XY: 74080

Gnomad4 AFR AF: 0.583

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.365

Alfa AF: 0.365 Hom.: 1378

Bravo AF: 0.391

Asia WGS AF: 0.341 AC: 1185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.23
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4375593; hg19: chr14-95067233;