rs2282679

Variant names:

• chr4-71742666-T-A
• rs2282679
• NM_000583.4:c.*26-796A>T

Your query was ambiguous. Multiple possible variants found:

• chr4-71742666-T-A
• chr4-71742666-T-C
• chr4-71742666-T-G

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-2 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -2 classification points (ACMG Germline Pathogenicity v2019). PM2BP4_Strong

The NM_000583.4(GC):c.*26-796A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GC NM_000583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.329
• Publications: 11 publications found

Genes affected

GC (HGNC:4187): (GC vitamin D binding protein) The protein encoded by this gene belongs to the albumin gene family. It is a multifunctional protein found in plasma, ascitic fluid, cerebrospinal fluid and on the surface of many cell types. It binds to vitamin D and its plasma metabolites and transports them to target tissues. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2011]

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AR/unknown gene) — PM2; Absent from gnomAD at well-covered site (MOI: unknown) (threshold 0.001) — PM2 moderate.
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_000583.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	GC NM_000583.4	MANE Select	c.*26-796A>T	intron	Intron 12 of 12	Prot: NP_000574.2
	GC NM_001204307.1		c.*26-796A>T	intron	Intron 13 of 13	Prot: NP_001191236.1 UniProt:
	GC NM_001204306.1		c.*26-796A>T	intron	Intron 13 of 13	Prot: NP_001191235.1 UniProt:

GC NM_000583.4

MANE Select

HGVSc / HGVSpc.*26-796A>T

Exon rankIntron 12 of 12

intron

Prot: NP_000574.2

GC NM_001204307.1

HGVSc / HGVSpc.*26-796A>T

Exon rankIntron 13 of 13

intron

Prot: NP_001191236.1UniProt: P02774-3

GC NM_001204306.1

HGVSc / HGVSpc.*26-796A>T

Exon rankIntron 13 of 13

intron

Prot: NP_001191235.1UniProt: P02774-1

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	GC ENST00000273951.13	TSL:1MANE Select	c.*26-796A>T	intron	Intron 12 of 12	Prot: ENSP00000273951.8 UniProt:
	GC ENST00000504199.5	TSL:1	c.*26-796A>T	intron	Intron 13 of 13	Prot: ENSP00000421725.1 UniProt:
	GC ENST00000513476.5	TSL:5	c.1396-796A>T	intron	Intron 11 of 11	Prot: ENSP00000426683.1 UniProt:

GC ENST00000273951.13

TSL:1MANE Select

HGVSc / HGVSpc.*26-796A>T

Exon rankIntron 12 of 12

intron

Prot: ENSP00000273951.8UniProt: P02774-1

GC ENST00000504199.5

TSL:1

HGVSc / HGVSpc.*26-796A>T

Exon rankIntron 13 of 13

intron

Prot: ENSP00000421725.1UniProt: P02774-3

GC ENST00000513476.5

TSL:5

HGVSc / HGVSpc.1396-796A>T

Exon rankIntron 11 of 11

intron

Prot: ENSP00000426683.1UniProt: D6RF35

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 2 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	2.6
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.9
DANN	Benign	0.77
GPN-Star LLR	N/A	-0.80
GPN-Star score	N/A	0.80
PhyloP100	Benign	0.33

Showing 7 of 7 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs2282679;

hg19: chr4-72608383;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar