6-38933460-G-A

Position:

• chr6-38933460-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001206927.2(DNAH8):​c.11457+1467G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 152,084 control chromosomes in the GnomAD database, including 37,744 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 0.70 (37744 hom., cov: 32)
• Consequence: DNAH8 NM_001206927.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.18

Genes affected

DNAH8 (HGNC:2952): (dynein axonemal heavy chain 8) The protein encoded by this gene is a heavy chain of an axonemal dynein involved in sperm and respiratory cilia motility. Axonemal dyneins generate force through hydrolysis of ATP and binding to microtubules. [provided by RefSeq, Jan 2012]

DNAH8-AS1 (HGNC:40188): (DNAH8 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2	c.11457+1467G>A		intron_variant		ENST00000327475.11
DNAH8-AS1	NR_038401.1	n.160+2833C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11	c.11457+1467G>A		intron_variant		5	NM_001206927.2	P2
DNAH8-AS1	ENST00000416948.1	n.152+2833C>T		intron_variant, non_coding_transcript_variant		2
DNAH8	ENST00000359357.7	c.10806+1467G>A		intron_variant		2		A2
DNAH8	ENST00000449981.6	c.11457+1467G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106200 AN: 151966 Hom.: 37709 Cov.: 32

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.649

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.699 AC: 106281 AN: 152084 Hom.: 37744 Cov.: 32 AF XY: 0.696 AC XY: 51765 AN XY: 74336

Gnomad4 AFR AF: 0.819

Gnomad4 AMR AF: 0.607

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.830

Gnomad4 SAS AF: 0.667

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.646

Alfa AF: 0.654 Hom.: 60605

Bravo AF: 0.700

Asia WGS AF: 0.706 AC: 2455 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.015
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs6458087; hg19: chr6-38901236;