chr4-71755148-C-CTATTTATTTATT

Variant names:

• chr4-71755148-C-CTATTTATTTATT
• rs58603194
• NM_000583.4:c.1035-53_1035-42dupAATAAATAAATA

Variant summary

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

The NM_000583.4(GC):​c.1035-53_1035-42dupAATAAATAAATA variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (1864 hom., cov: 0)
  • Exomes 𝑓: 0.078 (1902 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 (EAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GC	NM_000583.4	c.1035-53_1035-42dupAATAAATAAATA		intron_variant	Intron 8 of 12	ENST00000273951.13	NP_000574.2
GC	NM_001204307.1	c.1092-53_1092-42dupAATAAATAAATA		intron_variant	Intron 9 of 13		NP_001191236.1
GC	NM_001204306.1	c.1035-53_1035-42dupAATAAATAAATA		intron_variant	Intron 9 of 13		NP_001191235.1
GC	NM_001440458.1	c.1035-53_1035-42dupAATAAATAAATA		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.1035-53_1035-42dupAATAAATAAATA		intron_variant	Intron 8 of 12	1	NM_000583.4	ENSP00000273951.8

Frequencies

GnomAD3 genomes AF: 0.149 AC: 21625 AN: 144960 Hom.: 1860 Cov.: 0

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.0814

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0891

Gnomad MID AF: 0.116

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.137

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0781 AC: 22110 AN: 283204 Hom.: 1902 Cov.: 9 AF XY: 0.0814 AC XY: 12793 AN XY: 157196

African (AFR) AF: 0.0898 AC: 674 AN: 7504

American (AMR) AF: 0.0593 AC: 537 AN: 9054

Ashkenazi Jewish (ASJ) AF: 0.0587 AC: 403 AN: 6862

East Asian (EAS) AF: 0.177 AC: 1784 AN: 10106

South Asian (SAS) AF: 0.0809 AC: 1342 AN: 16588

European-Finnish (FIN) AF: 0.0676 AC: 1548 AN: 22904

Middle Eastern (MID) AF: 0.0584 AC: 112 AN: 1918

European-Non Finnish (NFE) AF: 0.0745 AC: 14642 AN: 196620

Other (OTH) AF: 0.0917 AC: 1068 AN: 11648

GnomAD4 genome AF: 0.149 AC: 21637 AN: 145048 Hom.: 1864 Cov.: 0 AF XY: 0.149 AC XY: 10466 AN XY: 70228

African (AFR) AF: 0.199 AC: 7785 AN: 39168

American (AMR) AF: 0.146 AC: 2104 AN: 14396

Ashkenazi Jewish (ASJ) AF: 0.0814 AC: 278 AN: 3416

East Asian (EAS) AF: 0.333 AC: 1636 AN: 4908

South Asian (SAS) AF: 0.126 AC: 560 AN: 4428

European-Finnish (FIN) AF: 0.0891 AC: 793 AN: 8902

Middle Eastern (MID) AF: 0.115 AC: 33 AN: 288

European-Non Finnish (NFE) AF: 0.120 AC: 8007 AN: 66642

Other (OTH) AF: 0.138 AC: 277 AN: 2010

Alfa AF: 0.114 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 (auto)

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;