rs1470457

chr2-135824278-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.84).
• BP6: Variant 2-135824278-A-G is Benign according to our data. Variant chr2-135824278-A-G is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCT	NM_002299.4	c.805-275T>C		intron_variant		ENST00000264162.7
LCT	XM_017004088.3	c.805-275T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCT	ENST00000264162.7	c.805-275T>C		intron_variant		1	NM_002299.4	P1

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

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.647

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.569

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.473

Alfa AF: 0.342 Hom.: 2867

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	7.1
Dann	Benign	0.76

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: rs1470457; hg19: chr2-136581848;