Variant 5-79119314-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_001713.3(BHMT):c.222C>T(p.Phe74Phe) variant causes a synonymous change. The variant allele was found at a frequency of 0.00164 in 1,614,152 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0083 ( 15 hom., cov: 33)

Exomes 𝑓: 0.00095 ( 14 hom. )

Consequence

BHMT
NM_001713.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.88

Variant links:

Genes affected

BHMT (HGNC:1047): (betaine--homocysteine S-methyltransferase) This gene encodes a cytosolic enzyme that catalyzes the conversion of betaine and homocysteine to dimethylglycine and methionine, respectively. Defects in this gene could lead to hyperhomocyst(e)inemia, but such a defect has not yet been observed. [provided by RefSeq, Jul 2008]

BHMT links:

BHMT (HGNC:):

BHMT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 5-79119314-C-T is Benign according to our data. Variant chr5-79119314-C-T is described in ClinVar as [Benign]. Clinvar id is 711926.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00834 (1270/152336) while in subpopulation AFR AF= 0.0285 (1183/41568). AF 95% confidence interval is 0.0271. There are 15 homozygotes in gnomad4. There are 621 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BHMT	NM_001713.3 linkuse as main transcript	c.222C>T	p.Phe74Phe	synonymous_variant	3/8	ENST00000274353.10	NP_001704.2	Q93088V9HWA4
LOC124901012	XR_007058837.1 linkuse as main transcript	n.2G>A		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BHMT	ENST00000274353.10 linkuse as main transcript	c.222C>T	p.Phe74Phe	synonymous_variant	3/8	1	NM_001713.3	ENSP00000274353.5	Q93088
BHMT	ENST00000524080.1 linkuse as main transcript	c.166+3415C>T		intron_variant		2		ENSP00000428240.1	E5RJH0
BHMT	ENST00000520703.1 linkuse as main transcript	n.299C>T		non_coding_transcript_exon_variant	3/3	2
DMGDH	ENST00000520388.5 linkuse as main transcript	n.491+1027G>A		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00830

AC:

1264

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0284

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00366

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00215

AC:

540

AN:

251386

Hom.:

AF XY:

0.00168

AC XY:

228

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.0268

Gnomad AMR exome

AF:

0.00185

Gnomad ASJ exome

AF:

0.000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000945

AC:

1382

AN:

1461816

Hom.:

Cov.:

AF XY:

0.000836

AC XY:

608

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.0292

Gnomad4 AMR exome

AF:

0.00208

Gnomad4 ASJ exome

AF:

0.00107

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000109

Gnomad4 OTH exome

AF:

0.00222

GnomAD4 genome

AF:

0.00834

AC:

1270

AN:

152336

Hom.:

Cov.:

AF XY:

0.00834

AC XY:

621

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0285

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00427

Hom.:

Bravo

AF:

0.0103

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.87

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over