rs730050

Positions:

• chr3-52314348-C-A
• chr3-52314348-C-G
• chr3-52314348-C-T

Variant summary

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

The XM_017006129.2(DNAH1):​c.-1812C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,094 control chromosomes in the GnomAD database, including 10,996 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 0.36 (10996 hom., cov: 32)
• Consequence: DNAH1 XM_017006129.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

Genes affected

DNAH1 (HGNC:2940): (dynein axonemal heavy chain 1) This gene encodes an inner dynein arm heavy chain that provides structural support between the radial spokes and the outer doublet of the sperm tail. Naturally occurring mutations in this gene are associated with primary ciliary dyskinesia and multiple morphological anomalies of the flagella that result in asthenozoospermia and male infertility. Mice with a homozygous knockout of the orthologous gene are viable but have reduced sperm motility and are infertile. [provided by RefSeq, Feb 2017]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH1	XM_017006129.2	c.-1812C>A		5_prime_UTR_variant	1/80		XP_016861618.1
DNAH1	XM_017006130.2	c.-1812C>A		5_prime_UTR_variant	1/79		XP_016861619.1
DNAH1	XM_017006131.2	c.-1812C>A		5_prime_UTR_variant	1/79		XP_016861620.1
		n.52314348C>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54349 AN: 151976 Hom.: 10990 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.357 AC: 54368 AN: 152094 Hom.: 10996 Cov.: 32 AF XY: 0.369 AC XY: 27409 AN XY: 74328

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.585

Gnomad4 SAS AF: 0.528

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.371

Alfa AF: 0.381 Hom.: 14565

Bravo AF: 0.347

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.14
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs730050; hg19: chr3-52348364;