rs12225692

chr11-83218535-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001300975.2(ANKRD42):c.587-6320C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0897 in 152,170 control chromosomes in the GnomAD database, including 800 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 0.090 (800 hom., cov: 32)
• Consequence: ANKRD42 NM_001300975.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.989

Genes affected

ANKRD42 (HGNC:26752): (ankyrin repeat domain 42) Predicted to enable NF-kappaB binding activity. Predicted to act upstream of or within positive regulation of NF-kappaB transcription factor activity and positive regulation of cytokine production involved in inflammatory response. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD42	NM_001300975.2	c.587-6320C>T		intron_variant		ENST00000533342.6
ANKRD42	NM_001300972.2	c.587-6320C>T		intron_variant
ANKRD42	NM_001300973.2	c.584-6320C>T		intron_variant
ANKRD42	NM_182603.4	c.503-6320C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD42	ENST00000533342.6	c.587-6320C>T		intron_variant		1	NM_001300975.2	A2
ANKRD42	ENST00000260047.10	c.584-6320C>T		intron_variant		1		P2
ANKRD42	ENST00000531895.5	c.587-6320C>T		intron_variant		1		A2
ANKRD42	ENST00000393392.6	c.503-6320C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0896 AC: 13622 AN: 152052 Hom.: 796 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.00989

Gnomad AMR AF: 0.0633

Gnomad ASJ AF: 0.0841

Gnomad EAS AF: 0.0296

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0283

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0703

Gnomad OTH AF: 0.0908

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

GnomAD4 genome AF: 0.0897 AC: 13647 AN: 152170 Hom.: 800 Cov.: 32 AF XY: 0.0863 AC XY: 6419 AN XY: 74414

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.0633

Gnomad4 ASJ AF: 0.0841

Gnomad4 EAS AF: 0.0293

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.0283

Gnomad4 NFE AF: 0.0703

Gnomad4 OTH AF: 0.0899

Alfa AF: 0.0763 Hom.: 147

Bravo AF: 0.0941

Asia WGS AF: 0.0820 AC: 285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	7.1
Dann	Benign	0.91

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

Publications

LitVar

Other links and lift over

dbSNP: rs12225692; hg19: chr11-82929577;