chr4-36282047-T-C

Variant names:

• chr4-36282047-T-C
• rs2109432275
• NM_001170700.3:c.271+18T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001170700.3(DTHD1):​c.271+18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000733 in 1,364,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: DTHD1 NM_001170700.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.322
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 4-36282047-T-C is Benign according to our data. Variant chr4-36282047-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1545834.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+18T>C		intron	N/A	NP_001164171.2	A0A1W2PR94
	DTHD1	NM_001136536.5		c.17+18T>C		intron	N/A	NP_001130008.2	Q6ZMT9-2
	DTHD1	NM_001378435.1		c.17+18T>C		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+18T>C		intron	N/A	ENSP00000492542.1	A0A1W2PR94
	DTHD1	ENST00000903021.1		c.271+18T>C		intron	N/A	ENSP00000573080.1
	DTHD1	ENST00000903020.1		c.271+18T>C		intron	N/A	ENSP00000573079.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.33e-7 AC: 1 AN: 1364376 Hom.: 0 Cov.: 28 AF XY: 0.00000149 AC XY: 1 AN XY: 672680

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

African (AFR) AF: 0.00 AC: 0 AN: 30488

American (AMR) AF: 0.00 AC: 0 AN: 33172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23762

East Asian (EAS) AF: 0.00 AC: 0 AN: 34852

South Asian (SAS) AF: 0.00 AC: 0 AN: 73314

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47506

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4956

European-Non Finnish (NFE) AF: 9.43e-7 AC: 1 AN: 1060068

Other (OTH) AF: 0.00 AC: 0 AN: 56258

⚠️ 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 Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely 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
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.47
PhyloP100		-0.32
PromoterAI		-0.0065	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2109432275; hg19: chr4-36283669;