dbSNP rs1470457: LCT:c.805-275T>C (chr2-135824278-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002299.4(LCT):c.805-275T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 152,044 control chromosomes in the GnomAD database, including 13,293 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.39 ( 13293 hom., cov: 32)

Consequence

LCT
NM_002299.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.162

Publications

4 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 2-135824278-A-G is Benign according to our data. Variant chr2-135824278-A-G is described in ClinVar as Benign. ClinVar VariationId is 1295578.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LCT	NM_002299.4 link	c.805-275T>C		intron_variant	Intron 3 of 16	ENST00000264162.7	NP_002290.2	P09848
LCT	XM_017004088.3 link	c.805-275T>C		intron_variant	Intron 3 of 14		XP_016859577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCT	ENST00000264162.7 link	c.805-275T>C		intron_variant	Intron 3 of 16	1	NM_002299.4	ENSP00000264162.2		P09848
LCT-AS1	ENST00000769912.1 link	n.400+3639A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.389

AC:

59092

AN:

151926

Hom.:

13263

Cov.:

show subpopulations

Gnomad AFR

AF:

0.540

Gnomad AMI

AF:

0.225

Gnomad AMR

AF:

0.507

Gnomad ASJ

AF:

0.647

Gnomad EAS

AF:

0.367

Gnomad SAS

AF:

0.570

Gnomad FIN

AF:

0.264

Gnomad MID

AF:

0.703

Gnomad NFE

AF:

0.264

Gnomad OTH

AF:

0.469

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

GnomAD4 genome

AF:

0.389

AC:

59179

AN:

152044

Hom.:

13293

Cov.:

AF XY:

0.398

AC XY:

29560

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.540

AC:

22400

AN:

41458

American (AMR)

AF:

0.506

AC:

7735

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.647

AC:

2245

AN:

3472

East Asian (EAS)

AF:

0.367

AC:

1898

AN:

5166

South Asian (SAS)

AF:

0.569

AC:

2741

AN:

4818

European-Finnish (FIN)

AF:

0.264

AC:

2793

AN:

10572

Middle Eastern (MID)

AF:

0.701

AC:

206

AN:

294

European-Non Finnish (NFE)

AF:

0.264

AC:

17959

AN:

67970

Other (OTH)

AF:

0.473

AC:

997

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1719

3439

5158

6878

8597

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

542

1084

1626

2168

2710

<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:

0.346

Hom.:

2984

Bravo

AF:

0.408

Asia WGS

AF:

0.495

AC:

1719

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.1

(source)

DANN

Benign

0.76

PhyloP100

0.16

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over