chr2-135818317-C-A

Position:

• chr2-135818317-C-A

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.987-256G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0497 in 152,144 control chromosomes in the GnomAD database, including 343 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.050 (343 hom., cov: 33)
• Consequence: LCT NM_002299.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.591

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 2-135818317-C-A is Benign according to our data. Variant chr2-135818317-C-A is described in ClinVar as [Benign]. Clinvar id is 1234217.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCT	NM_002299.4	c.987-256G>T		intron_variant		ENST00000264162.7
LCT	XM_017004088.3	c.987-256G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCT	ENST00000264162.7	c.987-256G>T		intron_variant		1	NM_002299.4	P1

Frequencies

GnomAD3 genomes AF: 0.0497 AC: 7552 AN: 152026 Hom.: 345 Cov.: 33

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0321

Gnomad ASJ AF: 0.0303

Gnomad EAS AF: 0.0603

Gnomad SAS AF: 0.0176

Gnomad FIN AF: 0.0224

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0213

Gnomad OTH AF: 0.0411

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

GnomAD4 genome AF: 0.0497 AC: 7560 AN: 152144 Hom.: 343 Cov.: 33 AF XY: 0.0487 AC XY: 3624 AN XY: 74392

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.0322

Gnomad4 ASJ AF: 0.0303

Gnomad4 EAS AF: 0.0607

Gnomad4 SAS AF: 0.0176

Gnomad4 FIN AF: 0.0224

Gnomad4 NFE AF: 0.0213

Gnomad4 OTH AF: 0.0417

Alfa AF: 0.0209 Hom.: 13

Bravo AF: 0.0527

Asia WGS AF: 0.0330 AC: 114 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

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.0
DANN	Benign	0.65

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: rs11884924; hg19: chr2-136575887;