4-36281691-A-T

Variant names:

• chr4-36281691-A-T
• rs7695130
• NM_001170700.3:c.-68A>T

Variant summary

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

The NM_001170700.3(DTHD1):​c.-68A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 1,081,706 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: DTHD1 NM_001170700.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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.-68A>T		5_prime_UTR	Exon 1 of 10	NP_001164171.2	A0A1W2PR94
	DTHD1	NM_001136536.5		c.-322A>T		5_prime_UTR	Exon 1 of 9	NP_001130008.2	Q6ZMT9-2
	DTHD1	NM_001378435.1		c.-322A>T		5_prime_UTR	Exon 1 of 8	NP_001365364.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTHD1	ENST00000639862.2	TSL:5 MANE Select	c.-68A>T		5_prime_UTR	Exon 1 of 10	ENSP00000492542.1	A0A1W2PR94
	DTHD1	ENST00000903021.1		c.-68A>T		5_prime_UTR	Exon 1 of 11	ENSP00000573080.1
	DTHD1	ENST00000903020.1		c.-68A>T		5_prime_UTR	Exon 1 of 11	ENSP00000573079.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000277 AC: 3 AN: 1081706 Hom.: 0 Cov.: 31 AF XY: 0.00000196 AC XY: 1 AN XY: 510706

⚠️ 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: 23050

American (AMR) AF: 0.00 AC: 0 AN: 8476

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14406

East Asian (EAS) AF: 0.00 AC: 0 AN: 26552

South Asian (SAS) AF: 0.00 AC: 0 AN: 19144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4542

European-Non Finnish (NFE) AF: 0.00000326 AC: 3 AN: 920480

Other (OTH) AF: 0.00 AC: 0 AN: 43894

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00131091), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.1
DANN	Benign	0.66
PhyloP100		0.039
PromoterAI		0.0036	Neutral

Splicing

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

Other links and lift over

dbSNP: rs7695130; hg19: chr4-36283313;