rs1047662

Positions:

• chr6-151101699-C-G
• chr6-151101699-C-T

Variant summary

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

The ENST00000367321.8(MTHFD1L):​c.*205C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,584 control chromosomes in the GnomAD database, including 1,146 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 0.11 (1145 hom., cov: 32)
  • Exomes 𝑓: 0.074 (1 hom.)
• Consequence: MTHFD1L ENST00000367321.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTHFD1L	NM_015440.5	c.*205C>G		3_prime_UTR_variant	28/28	ENST00000367321.8	NP_056255.2
LOC124901432	XR_007059813.1	n.342-13319G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.*205C>G		3_prime_UTR_variant	28/28	1	NM_015440.5	ENSP00000356290	P4
	ENST00000415477.1	n.576-13319G>C		intron_variant, non_coding_transcript_variant		5
MTHFD1L	ENST00000611279.4	c.*205C>G		3_prime_UTR_variant	28/28	5		ENSP00000478253	A1
MTHFD1L	ENST00000618312.4	c.*205C>G		3_prime_UTR_variant	28/28	5		ENSP00000479539

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16413 AN: 152036 Hom.: 1140 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0762

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.0812

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0701

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.0744 AC: 32 AN: 430 Hom.: 1 Cov.: 0 AF XY: 0.0654 AC XY: 17 AN XY: 260

Gnomad4 FIN exome AF: 0.0755

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.108 AC: 16427 AN: 152154 Hom.: 1145 Cov.: 32 AF XY: 0.113 AC XY: 8427 AN XY: 74374

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.0760

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.0812

Gnomad4 NFE AF: 0.0701

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0298 Hom.: 23

Bravo AF: 0.106

Asia WGS AF: 0.227 AC: 787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs1047662; hg19: chr6-151422835;