rs7349940

Variant names:

• chr6-151047780-T-A
• rs7349940
• NM_015440.5:c.2847+10663T>A

Variant summary

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

The NM_015440.5(MTHFD1L):​c.2847+10663T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,154 control chromosomes in the GnomAD database, including 1,648 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 0.10 (1648 hom., cov: 32)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTHFD1L	NM_015440.5	c.2847+10663T>A		intron_variant	Intron 26 of 27	ENST00000367321.8	NP_056255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.2847+10663T>A		intron_variant	Intron 26 of 27	1	NM_015440.5	ENSP00000356290.3
MTHFD1L	ENST00000611279.4	c.2850+10663T>A		intron_variant	Intron 26 of 27	5		ENSP00000478253.1
MTHFD1L	ENST00000618312.4	c.2652+10663T>A		intron_variant	Intron 26 of 27	5		ENSP00000479539.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15860 AN: 152036 Hom.: 1647 Cov.: 32

Gnomad AFR AF: 0.0239

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.0830

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.0962

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

GnomAD4 genome AF: 0.104 AC: 15857 AN: 152154 Hom.: 1648 Cov.: 32 AF XY: 0.107 AC XY: 7969 AN XY: 74380

African (AFR) AF: 0.0238 AC: 990 AN: 41530

American (AMR) AF: 0.0830 AC: 1268 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 381 AN: 3466

East Asian (EAS) AF: 0.590 AC: 3045 AN: 5158

South Asian (SAS) AF: 0.117 AC: 565 AN: 4824

European-Finnish (FIN) AF: 0.139 AC: 1474 AN: 10580

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7828 AN: 68002

Other (OTH) AF: 0.0971 AC: 205 AN: 2112

Alfa AF: 0.112 Hom.: 168

Bravo AF: 0.0991

Asia WGS AF: 0.313 AC: 1089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.74
DANN	Benign	0.57
PhyloP100		-0.19
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: rs7349940; hg19: chr6-151368916;