dbSNP rs2874874: LCT:c.986+1396T>G (chr2-135820624-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002299.4(LCT):c.986+1396T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,200 control chromosomes in the GnomAD database, including 2,417 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 0.16 ( 2416 hom., cov: 32)

Exomes 𝑓: 0.10 ( 1 hom. )

Consequence

LCT
NM_002299.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.33

Publications

5 publications found

Variant links:

Genes affected

LCT (HGNC:6530): (lactase) The protein encoded by this gene belongs to the glycosyl hydrolase 1 family of proteins. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme is integral to the plasma membrane and has both phlorizin hydrolase activity and lactase activity. Mutations in this gene are associated with congenital lactase deficiency. Polymorphisms in this gene are associated with lactase persistence, in which intestinal lactase activity persists at childhood levels into adulthood. [provided by RefSeq, Jan 2016]

LCT links:

LCT-AS1 (HGNC:40337): (LCT antisense RNA 1)

LCT-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002299.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCT	NM_002299.4	MANE Select	c.986+1396T>G		intron	N/A	NP_002290.2
	LCT-AS1	NR_045486.1		n.434A>C		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
LCT	ENST00000264162.7	TSL:1 MANE Select	c.986+1396T>G	intron	N/A	ENSP00000264162.2
LCT-AS1	ENST00000437007.2	TSL:2	n.434A>C	non_coding_transcript_exon	Exon 1 of 2
LCT-AS1	ENST00000769912.1		n.385A>C	non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24506

AN:

152022

Hom.:

2415

Cov.:

show subpopulations

Gnomad AFR

AF:

0.213

Gnomad AMI

AF:

0.0691

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.181

Gnomad EAS

AF:

0.203

Gnomad SAS

AF:

0.328

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.0983

Gnomad OTH

AF:

0.185

GnomAD4 exome

AF:

0.100

AC:

AN:

Hom.:

Cov.:

AF XY:

0.114

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.167

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.125

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.161

AC:

24538

AN:

152140

Hom.:

2416

Cov.:

AF XY:

0.169

AC XY:

12577

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.214

AC:

8866

AN:

41484

American (AMR)

AF:

0.250

AC:

3814

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.181

AC:

627

AN:

3468

East Asian (EAS)

AF:

0.204

AC:

1053

AN:

5170

South Asian (SAS)

AF:

0.327

AC:

1578

AN:

4822

European-Finnish (FIN)

AF:

0.130

AC:

1371

AN:

10586

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0984

AC:

6690

AN:

68018

Other (OTH)

AF:

0.185

AC:

391

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

998

1996

2994

3992

4990

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

270

540

810

1080

1350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.128

Hom.:

837

Bravo

AF:

0.168

Asia WGS

AF:

0.292

AC:

1016

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.4

(source)

DANN

Benign

0.66

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over