rs2236783

chr2-135836588-G-Achr2-135836588-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002299.4(LCT):c.582C>T(p.Thr194=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 1,613,296 control chromosomes in the GnomAD database, including 393,877 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (23867 hom., cov: 31)
  • Exomes 𝑓: 0.69 (370010 hom.)
• Consequence: LCT NM_002299.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0840

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 2-135836588-G-A is Benign according to our data. Variant chr2-135836588-G-A is described in ClinVar as [Benign]. Clinvar id is 331210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-135836588-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.084 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCT	NM_002299.4	c.582C>T	p.Thr194=	synonymous_variant	1/17	ENST00000264162.7
LCT	XM_017004088.3	c.582C>T	p.Thr194=	synonymous_variant	1/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCT	ENST00000264162.7	c.582C>T	p.Thr194=	synonymous_variant	1/17	1	NM_002299.4	P1

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77346 AN: 151828 Hom.: 23865 Cov.: 31

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.448

GnomAD3 exomes AF: 0.549 AC: 138019 AN: 251478 Hom.: 43334 AF XY: 0.552 AC XY: 75054 AN XY: 135912

Gnomad AFR exome AF: 0.214

Gnomad AMR exome AF: 0.400

Gnomad ASJ exome AF: 0.303

Gnomad EAS exome AF: 0.369

Gnomad SAS exome AF: 0.413

Gnomad FIN exome AF: 0.709

Gnomad NFE exome AF: 0.699

Gnomad OTH exome AF: 0.540

GnomAD4 exome AF: 0.688 AC: 1006069 AN: 1461352 Hom.: 370010 Cov.: 44 AF XY: 0.677 AC XY: 492412 AN XY: 727010

Gnomad4 AFR exome AF: 0.196

Gnomad4 AMR exome AF: 0.400

Gnomad4 ASJ exome AF: 0.304

Gnomad4 EAS exome AF: 0.383

Gnomad4 SAS exome AF: 0.419

Gnomad4 FIN exome AF: 0.707

Gnomad4 NFE exome AF: 0.761

Gnomad4 OTH exome AF: 0.614

GnomAD4 genome AF: 0.509 AC: 77360 AN: 151944 Hom.: 23867 Cov.: 31 AF XY: 0.500 AC XY: 37147 AN XY: 74248

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.711

Gnomad4 OTH AF: 0.443

Alfa AF: 0.598 Hom.: 17709

Bravo AF: 0.475

Asia WGS AF: 0.381 AC: 1327 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Lactose intolerance Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Congenital lactase deficiency Benign:1

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	-0.84
Cadd	Benign	2.2
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

Other links and lift over

dbSNP: rs2236783; hg19: chr2-136594158; COSMIC: COSV51464813; COSMIC: COSV51464813;