chr2-135819007-T-C

Variant names:

• chr2-135819007-T-C
• rs892715
• NM_002299.4:c.987-946A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002299.4(LCT):​c.987-946A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 152,010 control chromosomes in the GnomAD database, including 24,079 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (24079 hom., cov: 32)
• Consequence: LCT NM_002299.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.226
• Publications: 9 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 Gene-Disease associations (from GenCC):

• congenital lactase deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• 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 rank	MANE	Protein	UniProt
LCT	NM_002299.4	c.987-946A>G		intron_variant	Intron 5 of 16	ENST00000264162.7	NP_002290.2
LCT	XM_017004088.3	c.987-946A>G		intron_variant	Intron 5 of 14		XP_016859577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LCT	ENST00000264162.7	c.987-946A>G		intron_variant	Intron 5 of 16	1	NM_002299.4	ENSP00000264162.2

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77767 AN: 151892 Hom.: 24078 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.777

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.512 AC: 77770 AN: 152010 Hom.: 24079 Cov.: 32 AF XY: 0.503 AC XY: 37400 AN XY: 74318

African (AFR) AF: 0.217 AC: 9002 AN: 41470

American (AMR) AF: 0.415 AC: 6338 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1071 AN: 3466

East Asian (EAS) AF: 0.387 AC: 1995 AN: 5158

South Asian (SAS) AF: 0.379 AC: 1820 AN: 4802

European-Finnish (FIN) AF: 0.712 AC: 7536 AN: 10584

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.711 AC: 48288 AN: 67946

Other (OTH) AF: 0.446 AC: 943 AN: 2112

Alfa AF: 0.608 Hom.: 8403

Bravo AF: 0.480

Asia WGS AF: 0.386 AC: 1344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	5.7
DANN	Benign	0.90
PhyloP100		0.23
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: rs892715; hg19: chr2-136576577;