rs8039934

Positions:

• chr15-41205229-T-C

Variant summary

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

The NM_001286441.2(EXD1):​c.534+4272A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,110 control chromosomes in the GnomAD database, including 7,182 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 0.27 (7182 hom., cov: 32)
• Consequence: EXD1 NM_001286441.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147

Genes affected

EXD1 (HGNC:28507): (exonuclease 3'-5' domain containing 1) Predicted to enable RNA binding activity and protein homodimerization activity. Predicted to be involved in gene silencing by RNA and piRNA metabolic process. Predicted to be located in P granule. Predicted to be part of PET complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXD1	NM_001286441.2	c.534+4272A>G		intron_variant		ENST00000458580.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXD1	ENST00000458580.7	c.534+4272A>G		intron_variant		2	NM_001286441.2	P2
EXD1	ENST00000314992.9	c.360+4272A>G		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40397 AN: 151992 Hom.: 7156 Cov.: 32

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.0883

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.266 AC: 40468 AN: 152110 Hom.: 7182 Cov.: 32 AF XY: 0.264 AC XY: 19643 AN XY: 74372

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.0883

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.244

Alfa AF: 0.217 Hom.: 734

Bravo AF: 0.284

Asia WGS AF: 0.310 AC: 1075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs8039934; hg19: chr15-41497427;