rs10517371

chr4-36330671-T-C

Variant summary

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

The NM_001170700.3(DTHD1):c.2341-8441T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0672 in 152,166 control chromosomes in the GnomAD database, including 641 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 0.067 (641 hom., cov: 33)
• Consequence: DTHD1 NM_001170700.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0820

Genes affected

DTHD1 (HGNC:37261): (death domain containing 1) This gene encodes a protein which contains a death domain. Death domain-containing proteins function in signaling pathways and formation of signaling complexes, as well as the apoptosis pathway. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2012]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTHD1	NM_001170700.3	c.2341-8441T>C		intron_variant		ENST00000639862.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTHD1	ENST00000639862.2	c.2341-8441T>C		intron_variant		5	NM_001170700.3	P2
	ENST00000504344.1	n.331-18892A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0672 AC: 10211 AN: 152050 Hom.: 638 Cov.: 33

Gnomad AFR AF: 0.0778

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.0472

Gnomad FIN AF: 0.0163

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0353

Gnomad OTH AF: 0.0608

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

GnomAD4 genome AF: 0.0672 AC: 10229 AN: 152166 Hom.: 641 Cov.: 33 AF XY: 0.0697 AC XY: 5182 AN XY: 74386

Gnomad4 AFR AF: 0.0776

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.0337

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.0475

Gnomad4 FIN AF: 0.0163

Gnomad4 NFE AF: 0.0353

Gnomad4 OTH AF: 0.0653

Alfa AF: 0.0501 Hom.: 45

Bravo AF: 0.0843

Asia WGS AF: 0.110 AC: 382 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	3.0
Dann	Benign	0.67

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: rs10517371; hg19: chr4-36332293;