chr2-135788540-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002299.4(LCT):ā€‹c.5568T>Cā€‹(p.Ala1856=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 1,603,220 control chromosomes in the GnomAD database, including 442,835 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.60 ( 29596 hom., cov: 31)
Exomes š‘“: 0.74 ( 413239 hom. )

Consequence

LCT
NM_002299.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.140
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 2-135788540-A-G is Benign according to our data. Variant chr2-135788540-A-G is described in ClinVar as [Benign]. Clinvar id is 331164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-135788540-A-G is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.14 with no splicing effect.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LCTNM_002299.4 linkuse as main transcriptc.5568T>C p.Ala1856= synonymous_variant 17/17 ENST00000264162.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LCTENST00000264162.7 linkuse as main transcriptc.5568T>C p.Ala1856= synonymous_variant 17/171 NM_002299.4 P1

Frequencies

GnomAD3 genomes
AF:
0.597
AC:
90631
AN:
151862
Hom.:
29593
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.384
Gnomad AMI
AF:
0.783
Gnomad AMR
AF:
0.479
Gnomad ASJ
AF:
0.424
Gnomad EAS
AF:
0.443
Gnomad SAS
AF:
0.443
Gnomad FIN
AF:
0.747
Gnomad MID
AF:
0.335
Gnomad NFE
AF:
0.761
Gnomad OTH
AF:
0.537
GnomAD3 exomes
AF:
0.621
AC:
156029
AN:
251154
Hom.:
52340
AF XY:
0.622
AC XY:
84402
AN XY:
135746
show subpopulations
Gnomad AFR exome
AF:
0.379
Gnomad AMR exome
AF:
0.517
Gnomad ASJ exome
AF:
0.426
Gnomad EAS exome
AF:
0.442
Gnomad SAS exome
AF:
0.466
Gnomad FIN exome
AF:
0.748
Gnomad NFE exome
AF:
0.752
Gnomad OTH exome
AF:
0.614
GnomAD4 exome
AF:
0.739
AC:
1072495
AN:
1451240
Hom.:
413239
Cov.:
30
AF XY:
0.729
AC XY:
526552
AN XY:
722514
show subpopulations
Gnomad4 AFR exome
AF:
0.354
Gnomad4 AMR exome
AF:
0.512
Gnomad4 ASJ exome
AF:
0.428
Gnomad4 EAS exome
AF:
0.476
Gnomad4 SAS exome
AF:
0.476
Gnomad4 FIN exome
AF:
0.747
Gnomad4 NFE exome
AF:
0.802
Gnomad4 OTH exome
AF:
0.675
GnomAD4 genome
AF:
0.597
AC:
90662
AN:
151980
Hom.:
29596
Cov.:
31
AF XY:
0.586
AC XY:
43523
AN XY:
74260
show subpopulations
Gnomad4 AFR
AF:
0.384
Gnomad4 AMR
AF:
0.479
Gnomad4 ASJ
AF:
0.424
Gnomad4 EAS
AF:
0.442
Gnomad4 SAS
AF:
0.445
Gnomad4 FIN
AF:
0.747
Gnomad4 NFE
AF:
0.761
Gnomad4 OTH
AF:
0.532
Alfa
AF:
0.666
Hom.:
19342
Bravo
AF:
0.571
Asia WGS
AF:
0.443
AC:
1540
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Benign, no assertion criteria providedclinical testingJoint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+-- -
Benign, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxNov 12, 2018- -
Benign, criteria provided, single submitterclinical testingInvitaeFeb 01, 2024- -
Lactose intolerance Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Congenital lactase deficiency Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
2.4
DANN
Benign
0.62

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2278544; hg19: chr2-136546110; COSMIC: COSV51548301; COSMIC: COSV51548301; API