6-31900037-G-C

Variant names:

• chr6-31900037-G-C
• rs143020711
• NM_181842.3:c.1269C>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_181842.3(ZBTB12):​c.1269C>G​(p.Arg423Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000555 in 1,612,490 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00029 (1 hom.)
• Consequence: ZBTB12 NM_181842.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.63
• Publications: 1 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 6-31900037-G-C is Benign according to our data. Variant chr6-31900037-G-C is described in ClinVar as [Benign]. Clinvar id is 3025505.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.63 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB12	NM_181842.3	c.1269C>G	p.Arg423Arg	synonymous_variant	Exon 2 of 2	ENST00000375527.3	NP_862825.1
C2	NM_001282457.2	c.-64+2095G>C		intron_variant	Intron 1 of 13		NP_001269386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB12	ENST00000375527.3	c.1269C>G	p.Arg423Arg	synonymous_variant	Exon 2 of 2	1	NM_181842.3	ENSP00000364677.2
C2	ENST00000695637.1	c.-360+1762G>C		intron_variant	Intron 1 of 17			ENSP00000512074.1
C2	ENST00000497706.6	c.-64+2095G>C		intron_variant	Intron 1 of 14	5		ENSP00000417482.2
C2	ENST00000469372.5	c.-64+2095G>C		intron_variant	Intron 1 of 13	2		ENSP00000418923.1

Frequencies

GnomAD3 genomes AF: 0.00313 AC: 476 AN: 152266 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000774 AC: 193 AN: 249208 AF XY: 0.000510

Gnomad AFR exome AF: 0.0105

Gnomad AMR exome AF: 0.000492

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000445

Gnomad OTH exome AF: 0.000658

GnomAD4 exome AF: 0.000288 AC: 420 AN: 1460106 Hom.: 1 Cov.: 40 AF XY: 0.000212 AC XY: 154 AN XY: 726306

African (AFR) AF: 0.00876 AC: 293 AN: 33446

American (AMR) AF: 0.000537 AC: 24 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52672

Middle Eastern (MID) AF: 0.000377 AC: 2 AN: 5302

European-Non Finnish (NFE) AF: 0.0000675 AC: 75 AN: 1111648

Other (OTH) AF: 0.000431 AC: 26 AN: 60306

GnomAD4 genome AF: 0.00312 AC: 475 AN: 152384 Hom.: 2 Cov.: 32 AF XY: 0.00287 AC XY: 214 AN XY: 74524

African (AFR) AF: 0.0101 AC: 422 AN: 41592

American (AMR) AF: 0.00268 AC: 41 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68044

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.00101 Hom.: 1

Bravo AF: 0.00384

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ZBTB12: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.4
DANN	Benign	0.94
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism

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: rs143020711; hg19: chr6-31867814;