NM_001170700.3:c.887+901T>C

Variant names:

• chr4-36285492-T-C
• rs6837060
• NM_001170700.3:c.887+901T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

DTHD1 Gene-Disease associations (from GenCC):

• LCAT deficiency

  Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170700.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTHD1	NM_001170700.3	MANE Select	c.887+901T>C		intron	N/A	NP_001164171.2
	DTHD1	NM_001136536.5		c.17+3463T>C		intron	N/A	NP_001130008.2
	DTHD1	NM_001378435.1		c.17+3463T>C		intron	N/A	NP_001365364.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTHD1	ENST00000639862.2	TSL:5 MANE Select	c.887+901T>C		intron	N/A	ENSP00000492542.1
	DTHD1	ENST00000507598.5	TSL:1	c.632+901T>C		intron	N/A	ENSP00000424426.1
	DTHD1	ENST00000456874.3	TSL:1	c.512+901T>C		intron	N/A	ENSP00000401597.2

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

African (AFR) AF: 0.161 AC: 6680 AN: 41500

American (AMR) AF: 0.248 AC: 3786 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1190 AN: 3466

East Asian (EAS) AF: 0.0761 AC: 395 AN: 5188

South Asian (SAS) AF: 0.235 AC: 1131 AN: 4814

European-Finnish (FIN) AF: 0.159 AC: 1688 AN: 10584

Middle Eastern (MID) AF: 0.231 AC: 67 AN: 290

European-Non Finnish (NFE) AF: 0.248 AC: 16890 AN: 67974

Other (OTH) AF: 0.228 AC: 481 AN: 2110

Alfa AF: 0.229 Hom.: 931

Bravo AF: 0.215

Asia WGS AF: 0.150 AC: 527 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.9
DANN	Benign	0.91
PhyloP100		0.86
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6837060; hg19: chr4-36287114;