rs7695130

chr4-36281691-A-Cchr4-36281691-A-G

Variant summary

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

The NM_001170700.3(DTHD1):c.-68A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 1,233,632 control chromosomes in the GnomAD database, including 71,712 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 0.42 (17176 hom., cov: 33)
  • Exomes 𝑓: 0.31 (54536 hom.)
• Consequence: DTHD1 NM_001170700.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTHD1	NM_001170700.3	c.-68A>C		5_prime_UTR_variant	1/10	ENST00000639862.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTHD1	ENST00000639862.2	c.-68A>C		5_prime_UTR_variant	1/10	5	NM_001170700.3	P2
DTHD1	ENST00000357504.7	c.-322A>C		5_prime_UTR_variant	1/9	2		A2

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63918 AN: 152032 Hom.: 17120 Cov.: 33

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.386

GnomAD4 exome AF: 0.307 AC: 331701 AN: 1081482 Hom.: 54536 Cov.: 31 AF XY: 0.306 AC XY: 156208 AN XY: 510604

Gnomad4 AFR exome AF: 0.784

Gnomad4 AMR exome AF: 0.348

Gnomad4 ASJ exome AF: 0.368

Gnomad4 EAS exome AF: 0.123

Gnomad4 SAS exome AF: 0.278

Gnomad4 FIN exome AF: 0.187

Gnomad4 NFE exome AF: 0.301

Gnomad4 OTH exome AF: 0.332

GnomAD4 genome AF: 0.421 AC: 64043 AN: 152150 Hom.: 17176 Cov.: 33 AF XY: 0.412 AC XY: 30687 AN XY: 74410

Gnomad4 AFR AF: 0.765

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.373

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.386

Alfa AF: 0.284 Hom.: 3058

Bravo AF: 0.447

Asia WGS AF: 0.241 AC: 844 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	6.1
Dann	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7695130; hg19: chr4-36283313;