rs2073067

Variant names:

• chr6-150876016-C-A
• rs2073067
• NM_015440.5:c.228-74C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-150876016-C-A
• chr6-150876016-C-G

Variant summary

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

The NM_015440.5(MTHFD1L):​c.228-74C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000095 in 1,052,434 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: 9.5e-7 (0 hom.)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116
• Publications: 0 publications found

Genes affected

MTHFD1L (HGNC:21055): (methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1 like) The protein encoded by this gene is involved in the synthesis of tetrahydrofolate (THF) in the mitochondrion. THF is important in the de novo synthesis of purines and thymidylate and in the regeneration of methionine from homocysteine. Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jun 2011]

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=-0.94).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015440.5. 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
	MTHFD1L	NM_015440.5	MANE Select	c.228-74C>A		intron	N/A	NP_056255.2
	MTHFD1L	NM_001242767.2		c.228-74C>A		intron	N/A	NP_001229696.1	B7ZM99
	MTHFD1L	NM_001242768.2		c.30-74C>A		intron	N/A	NP_001229697.1	A0A087WVM4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD1L	ENST00000367321.8	TSL:1 MANE Select	c.228-74C>A		intron	N/A	ENSP00000356290.3	Q6UB35-1
	MTHFD1L	ENST00000367307.8	TSL:1	c.228-74C>A		intron	N/A	ENSP00000356276.4	Q6UB35-2
	MTHFD1L	ENST00000611279.4	TSL:5	c.228-74C>A		intron	N/A	ENSP00000478253.1	B7ZM99

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.50e-7 AC: 1 AN: 1052434 Hom.: 0 Cov.: 13 AF XY: 0.00000186 AC XY: 1 AN XY: 536708

⚠️ 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: 24728

American (AMR) AF: 0.00 AC: 0 AN: 35116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23004

East Asian (EAS) AF: 0.00 AC: 0 AN: 36754

South Asian (SAS) AF: 0.00 AC: 0 AN: 71336

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4920

European-Non Finnish (NFE) AF: 0.00000132 AC: 1 AN: 759280

Other (OTH) AF: 0.00 AC: 0 AN: 46350

⚠️ 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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.89
DANN	Benign	0.21
PhyloP100		-0.12

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: rs2073067; hg19: chr6-151197152;