4-71755148-CTATTTATTTATT-CTATTTATTTATTTATT

Variant names:

• chr4-71755148-C-CTATT
• rs58603194
• NM_000583.4:c.1035-45_1035-42dupAATA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000583.4(GC):​c.1035-45_1035-42dupAATA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.032 (113 hom., cov: 0)
  • Exomes 𝑓: 0.026 (191 hom.)
  • Failed GnomAD Quality Control
• Consequence: GC NM_000583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.440
• Publications: 0 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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GC	NM_000583.4	c.1035-45_1035-42dupAATA		intron_variant	Intron 8 of 12	ENST00000273951.13	NP_000574.2
GC	NM_001204307.1	c.1092-45_1092-42dupAATA		intron_variant	Intron 9 of 13		NP_001191236.1
GC	NM_001204306.1	c.1035-45_1035-42dupAATA		intron_variant	Intron 9 of 13		NP_001191235.1
GC	NM_001440458.1	c.1035-45_1035-42dupAATA		intron_variant	Intron 8 of 11		NP_001427387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GC	ENST00000273951.13	c.1035-45_1035-42dupAATA		intron_variant	Intron 8 of 12	1	NM_000583.4	ENSP00000273951.8

Frequencies

GnomAD3 genomes AF: 0.0316 AC: 4590 AN: 145118 Hom.: 114 Cov.: 0

Gnomad AFR AF: 0.0590

Gnomad AMI AF: 0.0536

Gnomad AMR AF: 0.0221

Gnomad ASJ AF: 0.0105

Gnomad EAS AF: 0.000609

Gnomad SAS AF: 0.00787

Gnomad FIN AF: 0.00864

Gnomad MID AF: 0.00968

Gnomad NFE AF: 0.0254

Gnomad OTH AF: 0.0336

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0261 AC: 7298 AN: 279600 Hom.: 191 Cov.: 9 AF XY: 0.0250 AC XY: 3876 AN XY: 155040

African (AFR) AF: 0.0478 AC: 359 AN: 7508

American (AMR) AF: 0.0137 AC: 123 AN: 8994

Ashkenazi Jewish (ASJ) AF: 0.0110 AC: 74 AN: 6708

East Asian (EAS) AF: 0.00109 AC: 11 AN: 10102

South Asian (SAS) AF: 0.00935 AC: 152 AN: 16250

European-Finnish (FIN) AF: 0.00808 AC: 182 AN: 22520

Middle Eastern (MID) AF: 0.0100 AC: 19 AN: 1898

European-Non Finnish (NFE) AF: 0.0313 AC: 6076 AN: 194128

Other (OTH) AF: 0.0263 AC: 302 AN: 11492

GnomAD4 genome AF: 0.0317 AC: 4599 AN: 145206 Hom.: 113 Cov.: 0 AF XY: 0.0314 AC XY: 2205 AN XY: 70294

African (AFR) AF: 0.0591 AC: 2317 AN: 39218

American (AMR) AF: 0.0220 AC: 317 AN: 14412

Ashkenazi Jewish (ASJ) AF: 0.0105 AC: 36 AN: 3422

East Asian (EAS) AF: 0.000611 AC: 3 AN: 4914

South Asian (SAS) AF: 0.00789 AC: 35 AN: 4436

European-Finnish (FIN) AF: 0.00864 AC: 77 AN: 8908

Middle Eastern (MID) AF: 0.0104 AC: 3 AN: 288

European-Non Finnish (NFE) AF: 0.0254 AC: 1696 AN: 66700

Other (OTH) AF: 0.0333 AC: 67 AN: 2012

Alfa AF: 0.0142 Hom.: 39

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs58603194; hg19: chr4-72620865;