dbSNP rs7579771: LCT:c.908-592A>T (chr2-135822690-T-A) – 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.908-592A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 157,946 control chromosomes in the GnomAD database, including 18,864 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 0.45 ( 18424 hom., cov: 33)

Exomes 𝑓: 0.34 ( 440 hom. )

Consequence

LCT
NM_002299.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.102

Publications

6 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:

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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=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
LCT	NM_002299.4 link	c.908-592A>T	intron_variant	Intron 4 of 16	ENST00000264162.7	NP_002290.2	P09848
LCT-AS1	NR_045486.1 link	n.1465T>A	non_coding_transcript_exon_variant	Exon 2 of 2
LCT	XM_017004088.3 link	c.908-592A>T	intron_variant	Intron 4 of 14		XP_016859577.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LCT	ENST00000264162.7 link	c.908-592A>T	intron_variant	Intron 4 of 16	1	NM_002299.4	ENSP00000264162.2	P09848
LCT-AS1	ENST00000437007.2 link	n.1465T>A	non_coding_transcript_exon_variant	Exon 2 of 2	2
LCT-AS1	ENST00000769912.1 link	n.400+2051T>A	intron_variant	Intron 1 of 1
LCT-AS1	ENST00000769913.1 link	n.555-261T>A	intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.452

AC:

68733

AN:

152020

Hom.:

18388

Cov.:

show subpopulations

Gnomad AFR

AF:

0.659

Gnomad AMI

AF:

0.225

Gnomad AMR

AF:

0.569

Gnomad ASJ

AF:

0.686

Gnomad EAS

AF:

0.612

Gnomad SAS

AF:

0.619

Gnomad FIN

AF:

0.288

Gnomad MID

AF:

0.753

Gnomad NFE

AF:

0.289

Gnomad OTH

AF:

0.523

GnomAD4 exome

AF:

0.337

AC:

1955

AN:

5808

Hom.:

440

Cov.:

AF XY:

0.350

AC XY:

1053

AN XY:

3006

show subpopulations

African (AFR)

AF:

0.800

AC:

AN:

American (AMR)

AF:

0.505

AC:

640

AN:

1268

Ashkenazi Jewish (ASJ)

AF:

0.833

AC:

AN:

East Asian (EAS)

AF:

0.526

AC:

AN:

156

South Asian (SAS)

AF:

0.531

AC:

290

AN:

546

European-Finnish (FIN)

AF:

0.300

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.231

AC:

815

AN:

3530

Other (OTH)

AF:

0.375

AC:

AN:

208

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

106

158

211

264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.452

AC:

68828

AN:

152138

Hom.:

18424

Cov.:

AF XY:

0.462

AC XY:

34360

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.659

AC:

27369

AN:

41504

American (AMR)

AF:

0.569

AC:

8695

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.686

AC:

2382

AN:

3472

East Asian (EAS)

AF:

0.613

AC:

3174

AN:

5176

South Asian (SAS)

AF:

0.618

AC:

2978

AN:

4818

European-Finnish (FIN)

AF:

0.288

AC:

3050

AN:

10590

Middle Eastern (MID)

AF:

0.759

AC:

223

AN:

294

European-Non Finnish (NFE)

AF:

0.289

AC:

19639

AN:

67982

Other (OTH)

AF:

0.527

AC:

1113

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1573

3145

4718

6290

7863

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

596

1192

1788

2384

2980

<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:

0.242

Hom.:

573

Bravo

AF:

0.478

Asia WGS

AF:

0.601

AC:

2091

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.2

(source)

DANN

Benign

0.74

PhyloP100

-0.10

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over