20-6006250-C-T

Variant names:

• chr20-6006250-C-T
• rs1476871319
• NM_019095.6:c.4C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_019095.6(CRLS1):​c.4C>T​(p.Leu2Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000183 in 1,092,738 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: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: CRLS1 NM_019095.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77
• Publications: 0 publications found

Genes affected

CRLS1 (HGNC:16148): (cardiolipin synthase 1) This gene encodes a member of the CDP-alcohol phosphatidyltransferase class-I family of proteins. The encoded enzyme catalyzes the synthesis of cardiolipin, a phospholipid component of mitochondrial membranes that is critical for mitochondrial function. [provided by RefSeq, Apr 2016]

ENSG00000286235 (HGNC:):

MCM8-AS1 (HGNC:51230): (MCM8 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP7: Synonymous conserved (PhyloP=1.77 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019095.6. 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
	CRLS1	NM_019095.6	MANE Select	c.4C>T	p.Leu2Leu	synonymous	Exon 1 of 7	NP_061968.1	Q9UJA2-1
	CRLS1	NM_001323563.2		c.-392C>T		5_prime_UTR	Exon 1 of 7	NP_001310492.1
	CRLS1	NM_001323562.2		c.-28+139C>T		intron	N/A	NP_001310491.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRLS1	ENST00000378863.9	TSL:1 MANE Select	c.4C>T	p.Leu2Leu	synonymous	Exon 1 of 7	ENSP00000368140.4	Q9UJA2-1
	CRLS1	ENST00000452938.5	TSL:1	c.4C>T	p.Leu2Leu	synonymous	Exon 1 of 6	ENSP00000416770.1	Q6NTG3
	ENSG00000286235	ENST00000652720.1		c.2431-3525C>T		intron	N/A	ENSP00000498784.1	A0A494C100

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000183 AC: 2 AN: 1092738 Hom.: 0 Cov.: 29 AF XY: 0.00000192 AC XY: 1 AN XY: 520218

African (AFR) AF: 0.00 AC: 0 AN: 22402

American (AMR) AF: 0.00 AC: 0 AN: 8018

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13972

East Asian (EAS) AF: 0.00 AC: 0 AN: 25428

South Asian (SAS) AF: 0.00 AC: 0 AN: 25046

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22230

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2900

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 929084

Other (OTH) AF: 0.0000458 AC: 2 AN: 43658

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	12
DANN	Benign	0.95
PhyloP100		1.8
PromoterAI		0.22	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1476871319; hg19: chr20-5986896;