rs11889147

Variant names:

• chr2-240692199-T-C
• rs11889147
• NM_198998.3:c.249T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-240692199-T-C
• chr2-240692199-T-G

Variant summary

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

The NM_198998.3(AQP12A):​c.249T>C​(p.Thr83Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 1,547,262 control chromosomes in the GnomAD database, including 4,133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (1150 hom., cov: 30)
  • Exomes 𝑓: 0.012 (2983 hom.)
• Consequence: AQP12A NM_198998.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.80
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BP6: Variant 2-240692199-T-C is Benign according to our data. Variant chr2-240692199-T-C is described in ClinVar as Benign. ClinVar VariationId is 1262883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 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.249T>C	p.Thr83Thr	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.249T>C	p.Thr83Thr	synonymous	Exon 2 of 4	ENSP00000337144.4	Q8IXF9

Frequencies

GnomAD3 genomes AF: 0.0497 AC: 6657 AN: 133904 Hom.: 1141 Cov.: 30

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0362

Gnomad ASJ AF: 0.0230

Gnomad EAS AF: 0.0187

Gnomad SAS AF: 0.0446

Gnomad FIN AF: 0.00611

Gnomad MID AF: 0.0292

Gnomad NFE AF: 0.00714

Gnomad OTH AF: 0.0392

GnomAD2 exomes AF: 0.0174 AC: 4115 AN: 236462 AF XY: 0.0160

Gnomad AFR exome AF: 0.117

Gnomad AMR exome AF: 0.0186

Gnomad ASJ exome AF: 0.0156

Gnomad EAS exome AF: 0.0123

Gnomad FIN exome AF: 0.000826

Gnomad NFE exome AF: 0.00475

Gnomad OTH exome AF: 0.0159

GnomAD4 exome AF: 0.0115 AC: 16263 AN: 1413292 Hom.: 2983 Cov.: 90 AF XY: 0.0117 AC XY: 8241 AN XY: 703162

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.167 AC: 4907 AN: 29426

American (AMR) AF: 0.0263 AC: 954 AN: 36228

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 492 AN: 24380

East Asian (EAS) AF: 0.0121 AC: 427 AN: 35308

South Asian (SAS) AF: 0.0323 AC: 2621 AN: 81110

European-Finnish (FIN) AF: 0.00168 AC: 86 AN: 51316

Middle Eastern (MID) AF: 0.0181 AC: 91 AN: 5020

European-Non Finnish (NFE) AF: 0.00513 AC: 5604 AN: 1092948

Other (OTH) AF: 0.0188 AC: 1081 AN: 57556

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0498 AC: 6678 AN: 133970 Hom.: 1150 Cov.: 30 AF XY: 0.0496 AC XY: 3228 AN XY: 65130

African (AFR) AF: 0.157 AC: 5318 AN: 33836

American (AMR) AF: 0.0362 AC: 443 AN: 12224

Ashkenazi Jewish (ASJ) AF: 0.0230 AC: 72 AN: 3136

East Asian (EAS) AF: 0.0185 AC: 72 AN: 3896

South Asian (SAS) AF: 0.0444 AC: 178 AN: 4012

European-Finnish (FIN) AF: 0.00611 AC: 59 AN: 9650

Middle Eastern (MID) AF: 0.0280 AC: 7 AN: 250

European-Non Finnish (NFE) AF: 0.00711 AC: 457 AN: 64300

Other (OTH) AF: 0.0392 AC: 72 AN: 1838

Alfa AF: 0.0258 Hom.: 181

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	-1.1
CADD	Benign	0.17
DANN	Benign	0.64
PhyloP100		-4.8
PromoterAI		-0.0021	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: rs11889147; hg19: chr2-241631616; COSMIC: COSV61836565; COSMIC: COSV61836565;