2-135822690-T-A

Variant names:

• chr2-135822690-T-A
• rs7579771
• NM_002299.4:c.908-592A>T

Variant summary

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

The NM_002299.4(LCT):​c.908-592A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 157,946 control chromosomes in the GnomAD database, including 18,864 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 0.45 (18424 hom., cov: 33)
  • Exomes 𝑓: 0.34 (440 hom.)
• Consequence: LCT NM_002299.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.653 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.908-592A>T		intron	N/A	NP_002290.2
	LCT-AS1	NR_045486.1		n.1465T>A		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCT	ENST00000264162.7	TSL:1 MANE Select	c.908-592A>T		intron	N/A	ENSP00000264162.2
	LCT-AS1	ENST00000437007.2	TSL:2	n.1465T>A		non_coding_transcript_exon	Exon 2 of 2
	LCT-AS1	ENST00000769912.1		n.400+2051T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68733 AN: 152020 Hom.: 18388 Cov.: 33

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.523

GnomAD4 exome AF: 0.337 AC: 1955 AN: 5808 Hom.: 440 Cov.: 0 AF XY: 0.350 AC XY: 1053 AN XY: 3006

African (AFR) AF: 0.800 AC: 16 AN: 20

American (AMR) AF: 0.505 AC: 640 AN: 1268

Ashkenazi Jewish (ASJ) AF: 0.833 AC: 15 AN: 18

East Asian (EAS) AF: 0.526 AC: 82 AN: 156

South Asian (SAS) AF: 0.531 AC: 290 AN: 546

European-Finnish (FIN) AF: 0.300 AC: 18 AN: 60

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.231 AC: 815 AN: 3530

Other (OTH) AF: 0.375 AC: 78 AN: 208

GnomAD4 genome AF: 0.452 AC: 68828 AN: 152138 Hom.: 18424 Cov.: 33 AF XY: 0.462 AC XY: 34360 AN XY: 74366

African (AFR) AF: 0.659 AC: 27369 AN: 41504

American (AMR) AF: 0.569 AC: 8695 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2382 AN: 3472

East Asian (EAS) AF: 0.613 AC: 3174 AN: 5176

South Asian (SAS) AF: 0.618 AC: 2978 AN: 4818

European-Finnish (FIN) AF: 0.288 AC: 3050 AN: 10590

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19639 AN: 67982

Other (OTH) AF: 0.527 AC: 1113 AN: 2110

Alfa AF: 0.242 Hom.: 573

Bravo AF: 0.478

Asia WGS AF: 0.601 AC: 2091 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.2
DANN	Benign	0.74
PhyloP100		-0.10
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: rs7579771; hg19: chr2-136580260;