chr2-135787878-AAC-A

Position:

• chr2-135787878-AAC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002299.4(LCT):​c.*444_*445del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 180,422 control chromosomes in the GnomAD database, including 3,397 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (2915 hom., cov: 28)
  • Exomes 𝑓: 0.16 (482 hom.)
• Consequence: LCT NM_002299.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 2.04

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 -10 ACMG points.

• BP6: Variant 2-135787878-AAC-A is Benign according to our data. Variant chr2-135787878-AAC-A is described in ClinVar as [Likely_benign]. Clinvar id is 331154.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCT	NM_002299.4	c.*444_*445del		3_prime_UTR_variant	17/17	ENST00000264162.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCT	ENST00000264162.7	c.*444_*445del		3_prime_UTR_variant	17/17	1	NM_002299.4	P1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28325 AN: 152032 Hom.: 2917 Cov.: 28

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.250

GnomAD4 exome AF: 0.163 AC: 4619 AN: 28272 Hom.: 482 AF XY: 0.169 AC XY: 2562 AN XY: 15120

Gnomad4 AFR exome AF: 0.189

Gnomad4 AMR exome AF: 0.205

Gnomad4 ASJ exome AF: 0.369

Gnomad4 EAS exome AF: 0.174

Gnomad4 SAS exome AF: 0.205

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.138

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome AF: 0.186 AC: 28338 AN: 152150 Hom.: 2915 Cov.: 28 AF XY: 0.188 AC XY: 13994 AN XY: 74390

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.253

Alfa AF: 0.180 Hom.: 339

Bravo AF: 0.193

Asia WGS AF: 0.185 AC: 643 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

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: rs140433552; hg19: chr2-136545448;