rs4302660

Positions:

• chr6-38877583-C-T

Variant summary

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

The NM_001206927.2(DNAH8):​c.7858+1755C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 151,964 control chromosomes in the GnomAD database, including 14,187 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 0.42 (14187 hom., cov: 32)
• Consequence: DNAH8 NM_001206927.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2	c.7858+1755C>T		intron_variant		ENST00000327475.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11	c.7858+1755C>T		intron_variant		5	NM_001206927.2	P2
DNAH8	ENST00000359357.7	c.7207+1755C>T		intron_variant		2		A2
DNAH8	ENST00000449981.6	c.7858+1755C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64155 AN: 151844 Hom.: 14145 Cov.: 32

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.423 AC: 64252 AN: 151964 Hom.: 14187 Cov.: 32 AF XY: 0.422 AC XY: 31344 AN XY: 74240

Gnomad4 AFR AF: 0.369

Gnomad4 AMR AF: 0.524

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.694

Gnomad4 SAS AF: 0.459

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.419

Alfa AF: 0.436 Hom.: 2336

Bravo AF: 0.432

Asia WGS AF: 0.574 AC: 1998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.78
DANN	Benign	0.76

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: rs4302660; hg19: chr6-38845359;