chr6-150892075-T-C

Variant names:

• chr6-150892075-T-C
• rs17349743
• NM_015440.5:c.780+4094T>C

Variant summary

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

The NM_015440.5(MTHFD1L):​c.780+4094T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,090 control chromosomes in the GnomAD database, including 7,136 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 0.30 (7136 hom., cov: 32)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.437
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTHFD1L	NM_015440.5	c.780+4094T>C		intron_variant	Intron 7 of 27	ENST00000367321.8	NP_056255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.780+4094T>C		intron_variant	Intron 7 of 27	1	NM_015440.5	ENSP00000356290.3

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45783 AN: 151974 Hom.: 7116 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.301 AC: 45843 AN: 152090 Hom.: 7136 Cov.: 32 AF XY: 0.300 AC XY: 22302 AN XY: 74338

African (AFR) AF: 0.255 AC: 10576 AN: 41476

American (AMR) AF: 0.427 AC: 6522 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 1239 AN: 3466

East Asian (EAS) AF: 0.225 AC: 1163 AN: 5180

South Asian (SAS) AF: 0.200 AC: 967 AN: 4826

European-Finnish (FIN) AF: 0.301 AC: 3182 AN: 10574

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21135 AN: 67988

Other (OTH) AF: 0.302 AC: 638 AN: 2112

Alfa AF: 0.307 Hom.: 32125

Bravo AF: 0.314

Asia WGS AF: 0.192 AC: 668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.47
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

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: rs17349743; hg19: chr6-151213211;