2-135787895-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002299.4(LCT):c.*429A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 195,960 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (21 hom., cov: 32)
  • Exomes 𝑓: 0.010 (10 hom.)
• Consequence: LCT NM_002299.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.0740

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-135787895-T-G is Benign according to our data. Variant chr2-135787895-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 331155.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-135787895-T-G is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0113 (1717/152242) while in subpopulation SAS AF= 0.0406 (196/4824). AF 95% confidence interval is 0.036. There are 21 homozygotes in gnomad4. There are 857 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCT	NM_002299.4	c.*429A>C		3_prime_UTR_variant	17/17	ENST00000264162.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCT	ENST00000264162.7	c.*429A>C		3_prime_UTR_variant	17/17	1	NM_002299.4	P1

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 1713 AN: 152124 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.0225

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00498

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0406

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00581

Gnomad OTH AF: 0.00957

GnomAD4 exome AF: 0.0101 AC: 440 AN: 43718 Hom.: 10 Cov.: 0 AF XY: 0.0127 AC XY: 297 AN XY: 23432

Gnomad4 AFR exome AF: 0.0224

Gnomad4 AMR exome AF: 0.00592

Gnomad4 ASJ exome AF: 0.0161

Gnomad4 EAS exome AF: 0.00105

Gnomad4 SAS exome AF: 0.0362

Gnomad4 FIN exome AF: 0.00372

Gnomad4 NFE exome AF: 0.00484

Gnomad4 OTH exome AF: 0.00596

GnomAD4 genome AF: 0.0113 AC: 1717 AN: 152242 Hom.: 21 Cov.: 32 AF XY: 0.0115 AC XY: 857 AN XY: 74456

Gnomad4 AFR AF: 0.0225

Gnomad4 AMR AF: 0.00497

Gnomad4 ASJ AF: 0.0187

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0406

Gnomad4 FIN AF: 0.00122

Gnomad4 NFE AF: 0.00581

Gnomad4 OTH AF: 0.00947

Alfa AF: 0.00868 Hom.: 4

Bravo AF: 0.0116

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Lactose intolerance Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Congenital lactase deficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.1
Dann	Benign	0.80

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

Other links and lift over

dbSNP: rs77631953; hg19: chr2-136545465;