chr4-36282039-C-CT

Variant names:

• chr4-36282039-C-CT
• rs372438791
• NM_001170700.3:c.271+18dupT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001170700.3(DTHD1):​c.271+18dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000153 in 1,518,898 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00069 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000093 (0 hom.)
• Consequence: DTHD1 NM_001170700.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.226
• 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: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 4-36282039-C-CT is Benign according to our data. Variant chr4-36282039-C-CT is described in ClinVar as Benign. ClinVar VariationId is 1167709.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTHD1	NM_001170700.3	MANE Select	c.271+18dupT		intron	N/A	NP_001164171.2	A0A1W2PR94
	DTHD1	NM_001136536.5		c.17+18dupT		intron	N/A	NP_001130008.2	Q6ZMT9-2
	DTHD1	NM_001378435.1		c.17+18dupT		intron	N/A	NP_001365364.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTHD1	ENST00000639862.2	TSL:5 MANE Select	c.271+10_271+11insT		intron	N/A	ENSP00000492542.1	A0A1W2PR94
	DTHD1	ENST00000903021.1		c.271+10_271+11insT		intron	N/A	ENSP00000573080.1
	DTHD1	ENST00000903020.1		c.271+10_271+11insT		intron	N/A	ENSP00000573079.1

Frequencies

GnomAD3 genomes AF: 0.000684 AC: 104 AN: 152016 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00239

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000331 AC: 44 AN: 133086 AF XY: 0.000341

Gnomad AFR exome AF: 0.00233

Gnomad AMR exome AF: 0.000250

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000112

Gnomad FIN exome AF: 0.000131

Gnomad NFE exome AF: 0.000231

Gnomad OTH exome AF: 0.000539

GnomAD4 exome AF: 0.0000929 AC: 127 AN: 1366764 Hom.: 0 Cov.: 29 AF XY: 0.0000861 AC XY: 58 AN XY: 673886

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00190 AC: 58 AN: 30478

American (AMR) AF: 0.000273 AC: 9 AN: 33004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23898

East Asian (EAS) AF: 0.0000288 AC: 1 AN: 34772

South Asian (SAS) AF: 0.000190 AC: 14 AN: 73786

European-Finnish (FIN) AF: 0.0000420 AC: 2 AN: 47620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5250

European-Non Finnish (NFE) AF: 0.0000320 AC: 34 AN: 1061572

Other (OTH) AF: 0.000160 AC: 9 AN: 56384

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000690 AC: 105 AN: 152134 Hom.: 0 Cov.: 32 AF XY: 0.000619 AC XY: 46 AN XY: 74360

African (AFR) AF: 0.00241 AC: 100 AN: 41522

American (AMR) AF: 0.000262 AC: 4 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67992

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000642

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs372438791; hg19: chr4-36283661;