rs11884924

Variant names:

• chr2-135818317-C-A
• rs11884924
• NM_002299.4:c.987-256G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-135818317-C-A
• chr2-135818317-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCT	NM_002299.4	MANE Select	c.987-256G>T		intron	N/A	NP_002290.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LCT	ENST00000264162.7	TSL:1 MANE Select	c.987-256G>T		intron	N/A	ENSP00000264162.2	P09848

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

African (AFR) AF: 0.115 AC: 4777 AN: 41494

American (AMR) AF: 0.0322 AC: 491 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0303 AC: 105 AN: 3468

East Asian (EAS) AF: 0.0607 AC: 314 AN: 5176

South Asian (SAS) AF: 0.0176 AC: 85 AN: 4820

European-Finnish (FIN) AF: 0.0224 AC: 237 AN: 10596

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0213 AC: 1450 AN: 68000

Other (OTH) AF: 0.0417 AC: 88 AN: 2112

Alfa AF: 0.0239 Hom.: 16

Bravo AF: 0.0527

Asia WGS AF: 0.0330 AC: 114 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.0
DANN	Benign	0.65
PhyloP100		-0.59
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: rs11884924; hg19: chr2-136575887;