chr6-35944492-A-G

Position:

• chr6-35944492-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_052961.4(SLC26A8):​c.2473-152T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 415,620 control chromosomes in the GnomAD database, including 5,447 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (4062 hom., cov: 31)
  • Exomes 𝑓: 0.073 (1385 hom.)
• Consequence: SLC26A8 NM_052961.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.150

Genes affected

SLC26A8 (HGNC:14468): (solute carrier family 26 member 8) This gene encodes a member of the SLC26 gene family of anion transporters. Family members are well conserved in gene structure and protein length yet have markedly different tissue expression patterns. The expression of this gene appears to be restricted to spermatocytes. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 6-35944492-A-G is Benign according to our data. Variant chr6-35944492-A-G is described in ClinVar as [Benign]. Clinvar id is 1280228.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A8	NM_052961.4	c.2473-152T>C		intron_variant		ENST00000490799.6	NP_443193.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A8	ENST00000490799.6	c.2473-152T>C		intron_variant		1	NM_052961.4	ENSP00000417638	P1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25451 AN: 149840 Hom.: 4040 Cov.: 31

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0643

Gnomad SAS AF: 0.0916

Gnomad FIN AF: 0.0583

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0586

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.0730 AC: 19407 AN: 265732 Hom.: 1385 AF XY: 0.0718 AC XY: 9847 AN XY: 137160

Gnomad4 AFR exome AF: 0.410

Gnomad4 AMR exome AF: 0.109

Gnomad4 ASJ exome AF: 0.103

Gnomad4 EAS exome AF: 0.0443

Gnomad4 SAS exome AF: 0.0574

Gnomad4 FIN exome AF: 0.0515

Gnomad4 NFE exome AF: 0.0570

Gnomad4 OTH exome AF: 0.0980

GnomAD4 genome AF: 0.170 AC: 25500 AN: 149888 Hom.: 4062 Cov.: 31 AF XY: 0.168 AC XY: 12258 AN XY: 73136

Gnomad4 AFR AF: 0.423

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.0641

Gnomad4 SAS AF: 0.0918

Gnomad4 FIN AF: 0.0583

Gnomad4 NFE AF: 0.0586

Gnomad4 OTH AF: 0.184

Alfa AF: 0.121 Hom.: 314

Bravo AF: 0.189

Asia WGS AF: 0.0980 AC: 339 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.6
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7746080; hg19: chr6-35912269;