6-31901896-C-T

Variant names:

• chr6-31901896-C-T
• rs2844455
• NM_181842.3:c.-80G>A

Variant summary

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

The NM_181842.3(ZBTB12):​c.-80G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 143,786 control chromosomes in the GnomAD database, including 2,536 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 0.17 (2536 hom., cov: 23)
  • Exomes 𝑓: 0.070 (0 hom.)
• Consequence: ZBTB12 NM_181842.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158
• Publications: 17 publications found

Genes affected

ZBTB12 (HGNC:19066): (zinc finger and BTB domain containing 12) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

C2 (HGNC:1248): (complement C2) Component C2 is a serum glycoprotein that functions as part of the classical pathway of the complement system. Activated C1 cleaves C2 into C2a and C2b. The serine proteinase C2a then combines with complement factor 4b to create the C3 or C5 convertase. Deficiency of C2 has been reported to associated with certain autoimmune diseases and SNPs in this gene have been associated with altered susceptibility to age-related macular degeneration. This gene localizes within the class III region of the MHC on the short arm of chromosome 6. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described in publications but their full-length sequence has not been determined.[provided by RefSeq, Mar 2009]

C2 Gene-Disease associations (from GenCC):

• complement component 2 deficiency

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181842.3. 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
	ZBTB12	NM_181842.3	MANE Select	c.-80G>A		5_prime_UTR	Exon 1 of 2	NP_862825.1	Q9Y330
	C2	NM_001178063.3		c.73+757C>T		intron	N/A	NP_001171534.1	P06681-2
	C2	NM_001282457.2		c.-64+3954C>T		intron	N/A	NP_001269386.1	B4DQI1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB12	ENST00000375527.3	TSL:1 MANE Select	c.-80G>A		5_prime_UTR	Exon 1 of 2	ENSP00000364677.2	Q9Y330
	C2	ENST00000695637.1		c.-360+3621C>T		intron	N/A	ENSP00000512074.1	A0A8Q3WKN5
	C2	ENST00000497706.6	TSL:5	c.-64+3954C>T		intron	N/A	ENSP00000417482.2	E9PDZ0

Frequencies

GnomAD3 genomes AF: 0.170 AC: 24329 AN: 143506 Hom.: 2532 Cov.: 23

Gnomad AFR AF: 0.0828

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.196

GnomAD4 exome AF: 0.0698 AC: 12 AN: 172 Hom.: 0 Cov.: 0 AF XY: 0.0603 AC XY: 7 AN XY: 116

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AF: 0.00 AC: 0 AN: 24

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0902 AC: 11 AN: 122

Other (OTH) AF: 0.0833 AC: 1 AN: 12

GnomAD4 genome AF: 0.169 AC: 24342 AN: 143614 Hom.: 2536 Cov.: 23 AF XY: 0.173 AC XY: 12080 AN XY: 69790

African (AFR) AF: 0.0826 AC: 3290 AN: 39812

American (AMR) AF: 0.281 AC: 4089 AN: 14532

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 904 AN: 3362

East Asian (EAS) AF: 0.285 AC: 1258 AN: 4414

South Asian (SAS) AF: 0.203 AC: 902 AN: 4444

European-Finnish (FIN) AF: 0.180 AC: 1697 AN: 9440

Middle Eastern (MID) AF: 0.230 AC: 64 AN: 278

European-Non Finnish (NFE) AF: 0.179 AC: 11582 AN: 64528

Other (OTH) AF: 0.195 AC: 387 AN: 1980

Alfa AF: 0.166 Hom.: 1588

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Uncertain	0.99
PhyloP100		-0.16
PromoterAI		-0.026	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97
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: rs2844455; hg19: chr6-31869673; COSMIC: COSV64994066; COSMIC: COSV64994066;