dbSNP rs8111071: RSPH6A:c.1653+104T>C (chr19-45804148-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_030785.4(RSPH6A):c.1653+104T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0746 in 851,118 control chromosomes in the GnomAD database, including 2,887 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 0.061 ( 391 hom., cov: 32)

Exomes 𝑓: 0.078 ( 2496 hom. )

Consequence

RSPH6A
NM_030785.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.82

Publications

32 publications found

Variant links:

Genes affected

RSPH6A (HGNC:14241): (radial spoke head 6 homolog A) The protein encoded by this gene is similar to a sea urchin radial spoke head protein. Radial spoke protein complexes form part of the axoneme of eukaryotic flagella and are located between the axoneme's outer ring of doublet microtubules and central pair of microtubules. In Chlamydomonas, radial spoke proteins are thought to regulate the activity of dynein and the symmetry of flagellar bending patterns. This gene maps to a region of chromosome 19 that is linked to primary ciliary dyskinesia-2 (CILD2). [provided by RefSeq, Jul 2008]

RSPH6A 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=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.09 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSPH6A	NM_030785.4 link	c.1653+104T>C		intron_variant	Intron 3 of 5	ENST00000221538.8	NP_110412.1	Q9H0K4
RSPH6A	XM_011527351.3 link	c.1653+104T>C		intron_variant	Intron 3 of 5		XP_011525653.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RSPH6A	ENST00000221538.8 link	c.1653+104T>C	intron_variant	Intron 3 of 5	1	NM_030785.4	ENSP00000221538.2	Q9H0K4
RSPH6A	ENST00000597055.1 link	c.1653+104T>C	intron_variant	Intron 3 of 5	1		ENSP00000472630.1	M0R2K1
RSPH6A	ENST00000600188.5 link	c.861+104T>C	intron_variant	Intron 2 of 4	2		ENSP00000471559.1	M0R103

Frequencies

GnomAD3 genomes

AF:

0.0606

AC:

9229

AN:

152170

Hom.:

391

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0144

Gnomad AMI

AF:

0.114

Gnomad AMR

AF:

0.0547

Gnomad ASJ

AF:

0.155

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0611

Gnomad FIN

AF:

0.0369

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.0919

Gnomad OTH

AF:

0.0774

GnomAD4 exome

AF:

0.0776

AC:

54258

AN:

698830

Hom.:

2496

AF XY:

0.0780

AC XY:

27925

AN XY:

358144

show subpopulations

African (AFR)

AF:

0.0125

AC:

221

AN:

17706

American (AMR)

AF:

0.0498

AC:

1123

AN:

22564

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

2221

AN:

15376

East Asian (EAS)

AF:

0.000234

AC:

AN:

34128

South Asian (SAS)

AF:

0.0710

AC:

3726

AN:

52472

European-Finnish (FIN)

AF:

0.0382

AC:

1294

AN:

33856

Middle Eastern (MID)

AF:

0.137

AC:

342

AN:

2498

European-Non Finnish (NFE)

AF:

0.0877

AC:

42612

AN:

486046

Other (OTH)

AF:

0.0793

AC:

2711

AN:

34184

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

2652

5304

7957

10609

13261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0606

AC:

9223

AN:

152288

Hom.:

391

Cov.:

AF XY:

0.0573

AC XY:

4265

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0143

AC:

596

AN:

41556

American (AMR)

AF:

0.0546

AC:

836

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.155

AC:

538

AN:

3466

East Asian (EAS)

AF:

0.000771

AC:

AN:

5188

South Asian (SAS)

AF:

0.0618

AC:

298

AN:

4824

European-Finnish (FIN)

AF:

0.0369

AC:

392

AN:

10614

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0919

AC:

6252

AN:

68016

Other (OTH)

AF:

0.0766

AC:

162

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

456

912

1367

1823

2279

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0805

Hom.:

1928

Bravo

AF:

0.0589

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.21

(source)

DANN

Benign

0.27

PhyloP100

-1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs8111071

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