chr2-135788089-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_002299.4(LCT):​c.*235C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000993 in 559,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00097 ( 0 hom. )

Consequence

LCT
NM_002299.4 3_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.01
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 2-135788089-G-A is Benign according to our data. Variant chr2-135788089-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 894024.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LCTNM_002299.4 linkuse as main transcriptc.*235C>T 3_prime_UTR_variant 17/17 ENST00000264162.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LCTENST00000264162.7 linkuse as main transcriptc.*235C>T 3_prime_UTR_variant 17/171 NM_002299.4 P1

Frequencies

GnomAD3 genomes
AF:
0.00106
AC:
162
AN:
152156
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00537
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000970
Gnomad OTH
AF:
0.00334
GnomAD4 exome
AF:
0.000966
AC:
393
AN:
406902
Hom.:
0
Cov.:
0
AF XY:
0.000921
AC XY:
200
AN XY:
217138
show subpopulations
Gnomad4 AFR exome
AF:
0.000346
Gnomad4 AMR exome
AF:
0.00467
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000372
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00113
Gnomad4 OTH exome
AF:
0.00129
GnomAD4 genome
AF:
0.00106
AC:
162
AN:
152274
Hom.:
0
Cov.:
32
AF XY:
0.00114
AC XY:
85
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.000168
Gnomad4 AMR
AF:
0.00536
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000970
Gnomad4 OTH
AF:
0.00331
Alfa
AF:
0.00109
Hom.:
0
Bravo
AF:
0.00133

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Congenital lactase deficiency Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
6.4
DANN
Benign
0.55

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: rs116002539; hg19: chr2-136545659; API