12-101067143-A-T

Variant names:

• chr12-101067143-A-T
• rs1849929
• NM_001286615.2:c.1313-12050A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001286615.2(ANO4):​c.1313-12050A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 313,748 control chromosomes in the GnomAD database, including 10,096 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3927 hom., cov: 32)
  • Exomes 𝑓: 0.26 (6169 hom.)
• Consequence: ANO4 NM_001286615.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.722
• Publications: 3 publications found

Genes affected

ANO4 (HGNC:23837): (anoctamin 4) Enables intracellular calcium activated chloride channel activity. Involved in chloride transport. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SNX5P2 (HGNC:41513): (sorting nexin 5 pseudogene 2)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO4	NM_001286615.2	c.1313-12050A>T		intron_variant	Intron 14 of 27	ENST00000392977.8	NP_001273544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO4	ENST00000392977.8	c.1313-12050A>T		intron_variant	Intron 14 of 27	2	NM_001286615.2	ENSP00000376703.3

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30337 AN: 151980 Hom.: 3931 Cov.: 32

Gnomad AFR AF: 0.0538

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.256 AC: 41352 AN: 161650 Hom.: 6169 AF XY: 0.264 AC XY: 22926 AN XY: 86906

African (AFR) AF: 0.0488 AC: 222 AN: 4548

American (AMR) AF: 0.225 AC: 1506 AN: 6698

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 963 AN: 4590

East Asian (EAS) AF: 0.532 AC: 4493 AN: 8450

South Asian (SAS) AF: 0.363 AC: 7519 AN: 20738

European-Finnish (FIN) AF: 0.248 AC: 2081 AN: 8392

Middle Eastern (MID) AF: 0.270 AC: 196 AN: 726

European-Non Finnish (NFE) AF: 0.225 AC: 22156 AN: 98366

Other (OTH) AF: 0.242 AC: 2216 AN: 9142

GnomAD4 genome AF: 0.199 AC: 30325 AN: 152098 Hom.: 3927 Cov.: 32 AF XY: 0.208 AC XY: 15426 AN XY: 74334

African (AFR) AF: 0.0537 AC: 2227 AN: 41506

American (AMR) AF: 0.231 AC: 3532 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 781 AN: 3472

East Asian (EAS) AF: 0.537 AC: 2773 AN: 5166

South Asian (SAS) AF: 0.388 AC: 1870 AN: 4820

European-Finnish (FIN) AF: 0.249 AC: 2623 AN: 10546

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15750 AN: 67982

Other (OTH) AF: 0.223 AC: 471 AN: 2108

Alfa AF: 0.204 Hom.: 501

Bravo AF: 0.190

Asia WGS AF: 0.408 AC: 1413 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.8
DANN	Benign	0.49
PhyloP100		0.72
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: rs1849929; hg19: chr12-101460921;