Variant chr12-6346853-CAACA-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001038.6(SCNN1A):c.*1016_*1019del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0364 in 152,154 control chromosomes in the GnomAD database, including 309 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 309 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SCNN1A
NM_001038.6 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.34

Variant links:

Genes affected

SCNN1A (HGNC:10599): (sodium channel epithelial 1 subunit alpha) Nonvoltage-gated, amiloride-sensitive, sodium channels control fluid and electrolyte transport across epithelia in many organs. These channels are heteromeric complexes consisting of 3 subunits: alpha, beta, and gamma. This gene encodes the alpha subunit, and mutations in this gene have been associated with pseudohypoaldosteronism type 1 (PHA1), a rare salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Apr 2009]

SCNN1A links:

LOC112268088 (HGNC:):

LOC112268088 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 12-6346853-CAACA-C is Benign according to our data. Variant chr12-6346853-CAACA-C is described in ClinVar as [Likely_benign]. Clinvar id is 310117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
SCNN1A	NM_001038.6 linkuse as main transcript	c.1016_1019del	3_prime_UTR_variant	13/13	ENST00000228916.7	NP_001029.1
LOC112268088	XR_002957396.2 linkuse as main transcript	n.707_710del	non_coding_transcript_exon_variant	2/2
SCNN1A	NM_001159575.2 linkuse as main transcript	c.1016_1019del	3_prime_UTR_variant	13/13		NP_001153047.1
SCNN1A	NM_001159576.2 linkuse as main transcript	c.1016_1019del	3_prime_UTR_variant	12/12		NP_001153048.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCNN1A	ENST00000228916.7 linkuse as main transcript	c.1016_1019del	3_prime_UTR_variant	13/13	1	NM_001038.6	ENSP00000228916	A2	P37088-1
SCNN1A	ENST00000360168.7 linkuse as main transcript	c.1016_1019del	3_prime_UTR_variant	12/12	1		ENSP00000353292	A2	P37088-2
SCNN1A	ENST00000540037.5 linkuse as main transcript	c.1016_1019del	3_prime_UTR_variant	11/11	1		ENSP00000440876

Frequencies

GnomAD3 genomes

AF:

0.0362

AC:

5502

AN:

152036

Hom.:

303

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0217

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.0124

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000794

Gnomad OTH

AF:

0.0274

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

490

Hom.:

AF XY:

0.00

AC XY:

AN XY:

306

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0364

AC:

5535

AN:

152154

Hom.:

309

Cov.:

AF XY:

0.0357

AC XY:

2658

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.121

Gnomad4 AMR

AF:

0.0217

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.0124

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000794

Gnomad4 OTH

AF:

0.0271

Alfa

AF:

0.0272

Hom.:

Bravo

AF:

0.0415

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Pseudohypoaldosteronism, type IB1, autosomal recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 22, 2021

- -

Bronchiectasis with or without elevated sweat chloride 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Familial Periodic Fever

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over