chr2-135821840-A-G

Position:

• chr2-135821840-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002299.4(LCT):​c.986+180T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 602,866 control chromosomes in the GnomAD database, including 307 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (226 hom., cov: 33)
  • Exomes 𝑓: 0.0038 (81 hom.)
• Consequence: LCT NM_002299.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.01

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-135821840-A-G is Benign according to our data. Variant chr2-135821840-A-G is described in ClinVar as [Benign]. Clinvar id is 1251276.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCT	NM_002299.4	c.986+180T>C		intron_variant		ENST00000264162.7
LCT-AS1	NR_045486.1	n.615A>G		non_coding_transcript_exon_variant	2/2
LCT	XM_017004088.3	c.986+180T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCT	ENST00000264162.7	c.986+180T>C		intron_variant		1	NM_002299.4	P1
LCT-AS1	ENST00000437007.1	n.615A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.0305 AC: 4642 AN: 152142 Hom.: 220 Cov.: 33

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0136

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0225

GnomAD4 exome AF: 0.00383 AC: 1727 AN: 450606 Hom.: 81 Cov.: 3 AF XY: 0.00323 AC XY: 780 AN XY: 241310

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.00644

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000343

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000133

Gnomad4 OTH exome AF: 0.00763

GnomAD4 genome AF: 0.0307 AC: 4675 AN: 152260 Hom.: 226 Cov.: 33 AF XY: 0.0294 AC XY: 2192 AN XY: 74458

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.0135

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.0222

Alfa AF: 0.0227 Hom.: 22

Bravo AF: 0.0363

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.3
DANN	Benign	0.53

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: rs112440562; hg19: chr2-136579410;