Genetic Variant ENST00000703602.1:c.*51-5186G>C (chr6-25732074-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000703602.1(ENSG00000290217):c.*51-5186G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,170,324 control chromosomes in the GnomAD database, including 90,241 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 0.40 ( 12515 hom., cov: 34)

Exomes 𝑓: 0.38 ( 77726 hom. )

Consequence

ENSG00000290217
ENST00000703602.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.216

Publications

6 publications found

Variant links:

Genes affected

ENSG00000290217 (HGNC:):

ENSG00000290217 links:

H2BC2P (HGNC:18719): (H2B clustered histone 2, pseudogene) Histones are basic nuclear proteins responsible for nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called nucleosomes. The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. This gene is a histone pseudogene found on chromosome 6. [provided by RefSeq, Oct 2015]

H2BC2P links:

SLC17A1 (HGNC:10929): (solute carrier family 17 member 1) Predicted to enable sialic acid transmembrane transporter activity. Involved in urate metabolic process and urate transport. Located in apical plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC17A1 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
H2BC2P		n.25732074G>C		intragenic_variant
SLC17A1	XM_017011201.3 link	c.*3-8281C>G		intron_variant	Intron 12 of 12		XP_016866690.2	Q14916-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
ENSG00000290217	ENST00000703602.1 link	c.*51-5186G>C	intron_variant	Intron 11 of 11		ENSP00000515390.1	A0A994J4C2
H2BC2P	ENST00000369177.5 link	n.89C>G	non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000308139	ENST00000831910.1 link	n.128C>G	non_coding_transcript_exon_variant	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.398

AC:

60466

AN:

152084

Hom.:

12500

Cov.:

show subpopulations

Gnomad AFR

AF:

0.466

Gnomad AMI

AF:

0.268

Gnomad AMR

AF:

0.356

Gnomad ASJ

AF:

0.482

Gnomad EAS

AF:

0.141

Gnomad SAS

AF:

0.353

Gnomad FIN

AF:

0.333

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.394

Gnomad OTH

AF:

0.429

GnomAD4 exome

AF:

0.383

AC:

390444

AN:

1018122

Hom.:

77726

Cov.:

AF XY:

0.382

AC XY:

193253

AN XY:

505498

show subpopulations

African (AFR)

AF:

0.463

AC:

10331

AN:

22304

American (AMR)

AF:

0.281

AC:

6884

AN:

24514

Ashkenazi Jewish (ASJ)

AF:

0.480

AC:

7621

AN:

15888

East Asian (EAS)

AF:

0.117

AC:

3606

AN:

30786

South Asian (SAS)

AF:

0.361

AC:

20551

AN:

56858

European-Finnish (FIN)

AF:

0.319

AC:

9544

AN:

29906

Middle Eastern (MID)

AF:

0.434

AC:

1661

AN:

3824

European-Non Finnish (NFE)

AF:

0.397

AC:

313940

AN:

791092

Other (OTH)

AF:

0.380

AC:

16306

AN:

42950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

10764

21527

32291

43054

53818

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9688

19376

29064

38752

48440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.397

AC:

60492

AN:

152202

Hom.:

12515

Cov.:

AF XY:

0.393

AC XY:

29255

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.466

AC:

19353

AN:

41526

American (AMR)

AF:

0.356

AC:

5440

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.482

AC:

1672

AN:

3470

East Asian (EAS)

AF:

0.140

AC:

725

AN:

5176

South Asian (SAS)

AF:

0.353

AC:

1703

AN:

4826

European-Finnish (FIN)

AF:

0.333

AC:

3523

AN:

10588

Middle Eastern (MID)

AF:

0.524

AC:

154

AN:

294

European-Non Finnish (NFE)

AF:

0.394

AC:

26785

AN:

67994

Other (OTH)

AF:

0.422

AC:

893

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1900

3800

5700

7600

9500

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

576

1152

1728

2304

2880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.254

Hom.:

616

Bravo

AF:

0.401

Asia WGS

AF:

0.255

AC:

890

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.70

(source)

DANN

Benign

0.63

PhyloP100

-0.22

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over