chr12-100748045-T-G

Variant names:

• chr12-100748045-T-G
• rs17030538
• ENST00000644049.1:c.358+7940T>G

Variant summary

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

The ENST00000549155.6(ANO4):​n.358+7940T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0523 in 152,174 control chromosomes in the GnomAD database, including 625 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 0.052 (625 hom., cov: 32)
• Consequence: ANO4 ENST00000549155.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301
• Publications: 1 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]

ANO4 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO4	XM_011537911.3	c.451+7940T>G		intron_variant	Intron 3 of 29		XP_011536213.2
ANO4	XM_011537912.3	c.451+7940T>G		intron_variant	Intron 3 of 29		XP_011536214.2
ANO4	XM_011537913.3	c.451+7940T>G		intron_variant	Intron 3 of 28		XP_011536215.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO4	ENST00000644049.1	c.358+7940T>G		intron_variant	Intron 3 of 29			ENSP00000494481.1
ANO4	ENST00000549155.6	n.358+7940T>G		intron_variant	Intron 3 of 10	2		ENSP00000449116.2

Frequencies

GnomAD3 genomes AF: 0.0522 AC: 7941 AN: 152056 Hom.: 622 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0241

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00553

Gnomad OTH AF: 0.0425

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0523 AC: 7964 AN: 152174 Hom.: 625 Cov.: 32 AF XY: 0.0509 AC XY: 3785 AN XY: 74418

African (AFR) AF: 0.169 AC: 7027 AN: 41486

American (AMR) AF: 0.0240 AC: 367 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0170 AC: 59 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4814

European-Finnish (FIN) AF: 0.00207 AC: 22 AN: 10614

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00553 AC: 376 AN: 68016

Other (OTH) AF: 0.0421 AC: 89 AN: 2116

Alfa AF: 0.0375 Hom.: 55

Bravo AF: 0.0607

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.53
DANN	Benign	0.64
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17030538; hg19: chr12-101141823;