chr2-135823784-T-G

Variant names:

• chr2-135823784-T-G
• rs895284
• NM_002299.4:c.907+117A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002299.4(LCT):​c.907+117A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.994 in 751,258 control chromosomes in the GnomAD database, including 371,402 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (73382 hom., cov: 29)
  • Exomes 𝑓: 1.0 (298020 hom.)
• Consequence: LCT NM_002299.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.158
• Publications: 0 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 2-135823784-T-G is Benign according to our data. Variant chr2-135823784-T-G is described in ClinVar as Benign. ClinVar VariationId is 1226280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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.907+117A>C		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.907+117A>C		intron	N/A	ENSP00000264162.2	P09848
	LCT-AS1	ENST00000769912.1		n.400+3145T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.982 AC: 149286 AN: 152060 Hom.: 73326 Cov.: 29

Gnomad AFR AF: 0.937

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.992

Gnomad ASJ AF: 0.995

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.987

GnomAD4 exome AF: 0.997 AC: 597505 AN: 599080 Hom.: 298020 AF XY: 0.998 AC XY: 321060 AN XY: 321736

African (AFR) AF: 0.930 AC: 15218 AN: 16364

American (AMR) AF: 0.996 AC: 34730 AN: 34852

Ashkenazi Jewish (ASJ) AF: 0.996 AC: 20075 AN: 20148

East Asian (EAS) AF: 1.00 AC: 32169 AN: 32170

South Asian (SAS) AF: 1.00 AC: 62896 AN: 62906

European-Finnish (FIN) AF: 1.00 AC: 47928 AN: 47928

Middle Eastern (MID) AF: 0.996 AC: 2504 AN: 2514

European-Non Finnish (NFE) AF: 1.00 AC: 350558 AN: 350604

Other (OTH) AF: 0.995 AC: 31427 AN: 31594

GnomAD4 genome AF: 0.982 AC: 149401 AN: 152178 Hom.: 73382 Cov.: 29 AF XY: 0.982 AC XY: 73035 AN XY: 74384

African (AFR) AF: 0.938 AC: 38910 AN: 41502

American (AMR) AF: 0.992 AC: 15162 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 3453 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5174 AN: 5174

South Asian (SAS) AF: 0.999 AC: 4811 AN: 4814

European-Finnish (FIN) AF: 1.00 AC: 10600 AN: 10600

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 67997 AN: 68014

Other (OTH) AF: 0.987 AC: 2089 AN: 2116

Alfa AF: 0.986 Hom.: 9571

Bravo AF: 0.979

Asia WGS AF: 0.996 AC: 3463 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.1
DANN	Benign	0.44
PhyloP100		0.16
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: rs895284; hg19: chr2-136581354;