2-240692248-C-T

Variant names:

• chr2-240692248-C-T
• rs76463197
• NM_198998.3:c.298C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_198998.3(AQP12A):​c.298C>T​(p.Leu100Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,577,426 control chromosomes in the GnomAD database, including 68,952 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (5112 hom., cov: 30)
  • Exomes 𝑓: 0.23 (63840 hom.)
• Consequence: AQP12A NM_198998.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.645
• Publications: 8 publications found

Genes affected

AQP12A (HGNC:19941): (aquaporin 12A) Predicted to enable channel activity. Predicted to be involved in transmembrane transport. Predicted to be integral component of membrane. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 2-240692248-C-T is Benign according to our data. Variant chr2-240692248-C-T is described in ClinVar as Benign. ClinVar VariationId is 1261959.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.645 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198998.3. 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
	AQP12A	NM_198998.3	MANE Select	c.298C>T	p.Leu100Leu	synonymous	Exon 2 of 4	NP_945349.1	Q8IXF9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP12A	ENST00000337801.9	TSL:1 MANE Select	c.298C>T	p.Leu100Leu	synonymous	Exon 2 of 4	ENSP00000337144.4	Q8IXF9

Frequencies

GnomAD3 genomes AF: 0.186 AC: 26849 AN: 144220 Hom.: 5113 Cov.: 30

Gnomad AFR AF: 0.0769

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.00296

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.201

GnomAD2 exomes AF: 0.199 AC: 47549 AN: 238416 AF XY: 0.204

Gnomad AFR exome AF: 0.0747

Gnomad AMR exome AF: 0.150

Gnomad ASJ exome AF: 0.218

Gnomad EAS exome AF: 0.00290

Gnomad FIN exome AF: 0.300

Gnomad NFE exome AF: 0.245

Gnomad OTH exome AF: 0.221

GnomAD4 exome AF: 0.228 AC: 327448 AN: 1433120 Hom.: 63840 Cov.: 122 AF XY: 0.228 AC XY: 162991 AN XY: 713360

African (AFR) AF: 0.0729 AC: 2298 AN: 31538

American (AMR) AF: 0.153 AC: 5913 AN: 38636

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 5613 AN: 25788

East Asian (EAS) AF: 0.00195 AC: 73 AN: 37356

South Asian (SAS) AF: 0.171 AC: 14326 AN: 83570

European-Finnish (FIN) AF: 0.296 AC: 15426 AN: 52064

Middle Eastern (MID) AF: 0.236 AC: 1165 AN: 4928

European-Non Finnish (NFE) AF: 0.245 AC: 269867 AN: 1100164

Other (OTH) AF: 0.216 AC: 12767 AN: 59076

GnomAD4 genome AF: 0.186 AC: 26838 AN: 144306 Hom.: 5112 Cov.: 30 AF XY: 0.187 AC XY: 13123 AN XY: 70260

African (AFR) AF: 0.0769 AC: 2899 AN: 37700

American (AMR) AF: 0.173 AC: 2363 AN: 13628

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 697 AN: 3392

East Asian (EAS) AF: 0.00297 AC: 14 AN: 4714

South Asian (SAS) AF: 0.156 AC: 706 AN: 4526

European-Finnish (FIN) AF: 0.292 AC: 3014 AN: 10336

Middle Eastern (MID) AF: 0.308 AC: 88 AN: 286

European-Non Finnish (NFE) AF: 0.247 AC: 16535 AN: 66840

Other (OTH) AF: 0.199 AC: 398 AN: 1998

Alfa AF: 0.223 Hom.: 1320

Asia WGS AF: 0.0900 AC: 299 AN: 3336

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	-0.56
CADD	Benign	7.0
DANN	Benign	0.55
PhyloP100		0.65
PromoterAI		0.0029	Neutral
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: rs76463197; hg19: chr2-241631665; COSMIC: COSV61837128; COSMIC: COSV61837128;