rs7695130

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr4-36281691-A-C
• chr4-36281691-A-G
• chr4-36281691-A-T

Variant summary

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

The NM_001170700.3(DTHD1):​c.-68A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 1,233,632 control chromosomes in the GnomAD database, including 71,712 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 0.42 (17176 hom., cov: 33)
  • Exomes 𝑓: 0.31 (54536 hom.)
• Consequence: DTHD1 NM_001170700.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390
• Publications: 9 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.758 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTHD1	NM_001170700.3	MANE Select	c.-68A>C		5_prime_UTR	Exon 1 of 10	NP_001164171.2
	DTHD1	NM_001136536.5		c.-322A>C		5_prime_UTR	Exon 1 of 9	NP_001130008.2
	DTHD1	NM_001378435.1		c.-322A>C		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>C		5_prime_UTR	Exon 1 of 10	ENSP00000492542.1
	DTHD1	ENST00000903021.1		c.-68A>C		5_prime_UTR	Exon 1 of 11	ENSP00000573080.1
	DTHD1	ENST00000903020.1		c.-68A>C		5_prime_UTR	Exon 1 of 11	ENSP00000573079.1

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63918 AN: 152032 Hom.: 17120 Cov.: 33

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.386

GnomAD4 exome AF: 0.307 AC: 331701 AN: 1081482 Hom.: 54536 Cov.: 31 AF XY: 0.306 AC XY: 156208 AN XY: 510604

African (AFR) AF: 0.784 AC: 18064 AN: 23048

American (AMR) AF: 0.348 AC: 2952 AN: 8474

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 5304 AN: 14402

East Asian (EAS) AF: 0.123 AC: 3274 AN: 26550

South Asian (SAS) AF: 0.278 AC: 5323 AN: 19142

European-Finnish (FIN) AF: 0.187 AC: 3966 AN: 21158

Middle Eastern (MID) AF: 0.306 AC: 1390 AN: 4542

European-Non Finnish (NFE) AF: 0.301 AC: 276846 AN: 920280

Other (OTH) AF: 0.332 AC: 14582 AN: 43886

GnomAD4 genome AF: 0.421 AC: 64043 AN: 152150 Hom.: 17176 Cov.: 33 AF XY: 0.412 AC XY: 30687 AN XY: 74410

African (AFR) AF: 0.765 AC: 31738 AN: 41466

American (AMR) AF: 0.390 AC: 5971 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1293 AN: 3468

East Asian (EAS) AF: 0.156 AC: 811 AN: 5184

South Asian (SAS) AF: 0.279 AC: 1346 AN: 4818

European-Finnish (FIN) AF: 0.171 AC: 1817 AN: 10610

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19770 AN: 68000

Other (OTH) AF: 0.386 AC: 812 AN: 2106

Alfa AF: 0.288 Hom.: 3485

Bravo AF: 0.447

Asia WGS AF: 0.241 AC: 844 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.1
DANN	Benign	0.68
PhyloP100		0.039
PromoterAI		0.038	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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; COSMIC: COSV107427909; COSMIC: COSV107427909;