Genetic Variant NM_002299.4:c.908-619A>G (chr2-135822717-T-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.908-619A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 156,696 control chromosomes in the GnomAD database, including 25,063 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 0.51 ( 24092 hom., cov: 32)

Exomes 𝑓: 0.62 ( 971 hom. )

Consequence

LCT
NM_002299.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0230

Publications

22 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=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
LCT	NM_002299.4 link	c.908-619A>G	intron_variant	Intron 4 of 16	ENST00000264162.7	NP_002290.2	P09848
LCT-AS1	NR_045486.1 link	n.1492T>C	non_coding_transcript_exon_variant	Exon 2 of 2
LCT	XM_017004088.3 link	c.908-619A>G	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.908-619A>G	intron_variant	Intron 4 of 16	1	NM_002299.4	ENSP00000264162.2	P09848
LCT-AS1	ENST00000437007.2 link	n.1492T>C	non_coding_transcript_exon_variant	Exon 2 of 2	2
LCT-AS1	ENST00000769912.1 link	n.400+2078T>C	intron_variant	Intron 1 of 1
LCT-AS1	ENST00000769913.1 link	n.555-234T>C	intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.512

AC:

77882

AN:

152036

Hom.:

24091

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.775

Gnomad AMR

AF:

0.415

Gnomad ASJ

AF:

0.309

Gnomad EAS

AF:

0.387

Gnomad SAS

AF:

0.379

Gnomad FIN

AF:

0.711

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.711

Gnomad OTH

AF:

0.451

GnomAD4 exome

AF:

0.619

AC:

2813

AN:

4542

Hom.:

971

Cov.:

AF XY:

0.607

AC XY:

1399

AN XY:

2306

show subpopulations

African (AFR)

AF:

0.150

AC:

AN:

American (AMR)

AF:

0.438

AC:

457

AN:

1044

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

AN:

East Asian (EAS)

AF:

0.357

AC:

AN:

South Asian (SAS)

AF:

0.400

AC:

171

AN:

428

European-Finnish (FIN)

AF:

0.633

AC:

AN:

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.737

AC:

2032

AN:

2756

Other (OTH)

AF:

0.615

AC:

AN:

148

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

127

169

211

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.512

AC:

77891

AN:

152154

Hom.:

24092

Cov.:

AF XY:

0.503

AC XY:

37438

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.219

AC:

9084

AN:

41514

American (AMR)

AF:

0.415

AC:

6338

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.309

AC:

1073

AN:

3472

East Asian (EAS)

AF:

0.386

AC:

2000

AN:

5176

South Asian (SAS)

AF:

0.381

AC:

1838

AN:

4828

European-Finnish (FIN)

AF:

0.711

AC:

7515

AN:

10566

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.711

AC:

48321

AN:

68002

Other (OTH)

AF:

0.447

AC:

945

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

1572

3144

4715

6287

7859

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

658

1316

1974

2632

3290

<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:

0.628

Hom.:

14350

Bravo

AF:

0.481

Asia WGS

AF:

0.390

AC:

1356

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.5

(source)

DANN

Benign

0.86

PhyloP100

-0.023

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