6-30303557-A-G

Variant names:

• chr6-30303557-A-G
• rs261946
• ENST00000426882.6:n.798-7320T>C

Variant summary

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

The ENST00000602319.2(HCG18):​n.989T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,186 control chromosomes in the GnomAD database, including 3,626 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 0.20 (3626 hom., cov: 31)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: HCG18 ENST00000602319.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 34 publications found

Genes affected

HCG18 (HGNC:31337): (HLA complex group 18)

HCG17 (HGNC:31339): (HLA complex group 17)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000602319.2. 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
	HCG18	NR_024052.2		n.1018-7320T>C		intron	N/A
	HCG18	NR_024053.2		n.804-7320T>C		intron	N/A
	HCG17	NR_052012.1		n.126+22452T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCG18	ENST00000426882.6	TSL:1	n.798-7320T>C		intron	N/A
	HCG18	ENST00000602319.2	TSL:6	n.989T>C		non_coding_transcript_exon	Exon 3 of 3
	HCG18	ENST00000412685.10	TSL:2	n.534-7320T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29758 AN: 152062 Hom.: 3625 Cov.: 31

Gnomad AFR AF: 0.0572

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.155

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.167 AC: 1 AN: 6

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.196 AC: 29770 AN: 152180 Hom.: 3626 Cov.: 31 AF XY: 0.199 AC XY: 14781 AN XY: 74388

African (AFR) AF: 0.0573 AC: 2381 AN: 41566

American (AMR) AF: 0.197 AC: 3018 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 492 AN: 3472

East Asian (EAS) AF: 0.275 AC: 1426 AN: 5182

South Asian (SAS) AF: 0.108 AC: 519 AN: 4814

European-Finnish (FIN) AF: 0.351 AC: 3706 AN: 10564

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17601 AN: 67972

Other (OTH) AF: 0.154 AC: 325 AN: 2116

Alfa AF: 0.228 Hom.: 12944

Bravo AF: 0.179

Asia WGS AF: 0.152 AC: 528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.2
DANN	Benign	0.59
PhyloP100		1.1

Splicing

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.

Other links and lift over

dbSNP: rs261946;

hg19: chr6-30271334;