dbSNP rs2322812: LCT:c.986+1550T>C (chr2-135820470-A-G) – 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+1550T>C 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 152,424 control chromosomes in the GnomAD database, including 2,425 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.16 ( 2422 hom., cov: 32)

Exomes 𝑓: 0.14 ( 3 hom. )

Consequence

LCT
NM_002299.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.370

Publications

0 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=-0.82).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.313 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCT	NM_002299.4	MANE Select	c.986+1550T>C		intron	N/A	NP_002290.2
	LCT-AS1	NR_045486.1		n.280A>G		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LCT	ENST00000264162.7	TSL:1 MANE Select	c.986+1550T>C	intron	N/A	ENSP00000264162.2	P09848
LCT-AS1	ENST00000437007.2	TSL:2	n.280A>G	non_coding_transcript_exon	Exon 1 of 2
LCT-AS1	ENST00000769912.1		n.231A>G	non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24527

AN:

152064

Hom.:

2421

Cov.:

show subpopulations

Gnomad AFR

AF:

0.213

Gnomad AMI

AF:

0.0691

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.180

Gnomad EAS

AF:

0.204

Gnomad SAS

AF:

0.327

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.293

Gnomad NFE

AF:

0.0983

Gnomad OTH

AF:

0.185

GnomAD4 exome

AF:

0.136

AC:

AN:

242

Hom.:

Cov.:

AF XY:

0.146

AC XY:

AN XY:

178

show subpopulations

African (AFR)

AF:

0.167

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.250

AC:

AN:

European-Finnish (FIN)

AF:

0.125

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.113

AC:

AN:

204

Other (OTH)

AF:

0.438

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.161

AC:

24559

AN:

152182

Hom.:

2422

Cov.:

AF XY:

0.169

AC XY:

12605

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.214

AC:

8881

AN:

41526

American (AMR)

AF:

0.250

AC:

3817

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.180

AC:

625

AN:

3468

East Asian (EAS)

AF:

0.204

AC:

1056

AN:

5172

South Asian (SAS)

AF:

0.326

AC:

1575

AN:

4824

European-Finnish (FIN)

AF:

0.130

AC:

1379

AN:

10598

Middle Eastern (MID)

AF:

0.288

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0984

AC:

6688

AN:

68000

Other (OTH)

AF:

0.185

AC:

391

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1031

2063

3094

4126

5157

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:

0.140

Hom.:

227

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

-0.82

CADD

Benign

0.91

(source)

DANN

Benign

0.65

PhyloP100

-0.37

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over