NM_001170700.3:c.888-1573A>G

Variant names:

• chr4-36288800-A-G
• rs10517375
• NM_001170700.3:c.888-1573A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001170700.3(DTHD1):​c.888-1573A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0779 in 152,276 control chromosomes in the GnomAD database, including 892 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 0.078 (892 hom., cov: 32)
• Consequence: DTHD1 NM_001170700.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• Publications: 0 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTHD1	NM_001170700.3	c.888-1573A>G		intron_variant	Intron 2 of 9	ENST00000639862.2	NP_001164171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTHD1	ENST00000639862.2	c.888-1573A>G		intron_variant	Intron 2 of 9	5	NM_001170700.3	ENSP00000492542.1
DTHD1	ENST00000507598.5	c.633-1573A>G		intron_variant	Intron 1 of 8	1		ENSP00000424426.1
DTHD1	ENST00000456874.3	c.513-1573A>G		intron_variant	Intron 1 of 8	1		ENSP00000401597.2
DTHD1	ENST00000357504.7	c.18-1573A>G		intron_variant	Intron 1 of 8	2		ENSP00000350103.3

Frequencies

GnomAD3 genomes AF: 0.0777 AC: 11823 AN: 152158 Hom.: 888 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0867

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.0621

Gnomad SAS AF: 0.00745

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0267

Gnomad OTH AF: 0.0546

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

GnomAD4 genome AF: 0.0779 AC: 11868 AN: 152276 Hom.: 892 Cov.: 32 AF XY: 0.0758 AC XY: 5645 AN XY: 74462

African (AFR) AF: 0.196 AC: 8140 AN: 41514

American (AMR) AF: 0.0870 AC: 1331 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3472

East Asian (EAS) AF: 0.0623 AC: 323 AN: 5188

South Asian (SAS) AF: 0.00787 AC: 38 AN: 4830

European-Finnish (FIN) AF: 0.00273 AC: 29 AN: 10628

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0267 AC: 1816 AN: 68030

Other (OTH) AF: 0.0540 AC: 114 AN: 2110

Alfa AF: 0.0369 Hom.: 625

Bravo AF: 0.0890

Asia WGS AF: 0.0360 AC: 127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.4
DANN	Benign	0.71
PhyloP100		1.2
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: rs10517375; hg19: chr4-36290422;