rs6837060

Positions:

• chr4-36285492-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.887+901T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,092 control chromosomes in the GnomAD database, including 3,702 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 0.21 (3702 hom., cov: 31)
• Consequence: DTHD1 NM_001170700.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.864

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=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTHD1	NM_001170700.3	c.887+901T>C		intron_variant		ENST00000639862.2	NP_001164171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTHD1	ENST00000639862.2	c.887+901T>C		intron_variant		5	NM_001170700.3	ENSP00000492542	P2
DTHD1	ENST00000456874.3	c.512+901T>C		intron_variant		1		ENSP00000401597	A2
DTHD1	ENST00000507598.5	c.632+901T>C		intron_variant		1		ENSP00000424426	A2
DTHD1	ENST00000357504.7	c.17+3463T>C		intron_variant		2		ENSP00000350103	A2

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32649 AN: 151974 Hom.: 3698 Cov.: 31

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.0758

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.215 AC: 32661 AN: 152092 Hom.: 3702 Cov.: 31 AF XY: 0.212 AC XY: 15767 AN XY: 74364

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.0761

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.228

Alfa AF: 0.231 Hom.: 923

Bravo AF: 0.215

Asia WGS AF: 0.150 AC: 527 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.9
DANN	Benign	0.91

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: rs6837060; hg19: chr4-36287114;