rs4740919

Positions:

• chr9-7854892-G-A
• chr9-7854892-G-C
• chr9-7854892-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000469050.1(DMAC1):​n.83-20886C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 151,904 control chromosomes in the GnomAD database, including 5,134 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 0.25 (5134 hom., cov: 32)
• Consequence: DMAC1 ENST00000469050.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540

Genes affected

DMAC1 (HGNC:30536): (distal membrane arm assembly component 1) Involved in mitochondrial respiratory chain complex I assembly. Located in mitochondrial inner membrane. Colocalizes with mitochondrial respiratory chain complex I. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMAC1	ENST00000469050.1	n.83-20886C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38449 AN: 151788 Hom.: 5123 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.253 AC: 38483 AN: 151904 Hom.: 5134 Cov.: 32 AF XY: 0.255 AC XY: 18956 AN XY: 74258

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.352

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.237

Alfa AF: 0.225 Hom.: 1069

Bravo AF: 0.249

Asia WGS AF: 0.293 AC: 1022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4740919; hg19: chr9-7854892;