2-135824278-A-G

Variant names:

• chr2-135824278-A-G
• rs1470457
• NM_002299.4:c.805-275T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002299.4(LCT):​c.805-275T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 152,044 control chromosomes in the GnomAD database, including 13,293 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.39 (13293 hom., cov: 32)
• Consequence: LCT NM_002299.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.162
• Publications: 4 publications found

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]

LCT-AS1 (HGNC:40337): (LCT antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 2-135824278-A-G is Benign according to our data. Variant chr2-135824278-A-G is described in ClinVar as Benign. ClinVar VariationId is 1295578.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002299.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCT	NM_002299.4	MANE Select	c.805-275T>C		intron	N/A	NP_002290.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCT	ENST00000264162.7	TSL:1 MANE Select	c.805-275T>C		intron	N/A	ENSP00000264162.2
	LCT-AS1	ENST00000769912.1		n.400+3639A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59092 AN: 151926 Hom.: 13263 Cov.: 32

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.469

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.389 AC: 59179 AN: 152044 Hom.: 13293 Cov.: 32 AF XY: 0.398 AC XY: 29560 AN XY: 74326

African (AFR) AF: 0.540 AC: 22400 AN: 41458

American (AMR) AF: 0.506 AC: 7735 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2245 AN: 3472

East Asian (EAS) AF: 0.367 AC: 1898 AN: 5166

South Asian (SAS) AF: 0.569 AC: 2741 AN: 4818

European-Finnish (FIN) AF: 0.264 AC: 2793 AN: 10572

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17959 AN: 67970

Other (OTH) AF: 0.473 AC: 997 AN: 2110

Alfa AF: 0.346 Hom.: 2984

Bravo AF: 0.408

Asia WGS AF: 0.495 AC: 1719 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.1
DANN	Benign	0.76
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1470457; hg19: chr2-136581848;