Variant 17-44248849-G-GT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000342.4(SLC4A1):c.*1608_*1609insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.055 ( 939 hom., cov: 0)

Exomes 𝑓: 0.0012 ( 6 hom. )

Consequence

SLC4A1
NM_000342.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:3

Conservation

PhyloP100: -0.697

Variant links:

Genes affected

SLC4A1 (HGNC:11027): (solute carrier family 4 member 1 (Diego blood group)) The protein encoded by this gene is part of the anion exchanger (AE) family and is expressed in the erythrocyte plasma membrane, where it functions as a chloride/bicarbonate exchanger involved in carbon dioxide transport from tissues to lungs. The protein comprises two domains that are structurally and functionally distinct. The N-terminal 40kDa domain is located in the cytoplasm and acts as an attachment site for the red cell skeleton by binding ankyrin. The glycosylated C-terminal membrane-associated domain contains 12-14 membrane spanning segments and carries out the stilbene disulphonate-sensitive exchange transport of anions. The cytoplasmic tail at the extreme C-terminus of the membrane domain binds carbonic anhydrase II. The encoded protein associates with the red cell membrane protein glycophorin A and this association promotes the correct folding and translocation of the exchanger. This protein is predominantly dimeric but forms tetramers in the presence of ankyrin. Many mutations in this gene are known in man, and these mutations can lead to two types of disease: destabilization of red cell membrane leading to hereditary spherocytosis, and defective kidney acid secretion leading to distal renal tubular acidosis. Other mutations that do not give rise to disease result in novel blood group antigens, which form the Diego blood group system. Southeast Asian ovalocytosis (SAO, Melanesian ovalocytosis) results from the heterozygous presence of a deletion in the encoded protein and is common in areas where Plasmodium falciparum malaria is endemic. One null mutation in this gene is known, resulting in very severe anemia and nephrocalcinosis. [provided by RefSeq, Jul 2008]

SLC4A1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
SLC4A1	NM_000342.4 linkuse as main transcript	c.1608_1609insA	3_prime_UTR_variant	20/20	ENST00000262418.12
SLC4A1	XM_005257593.6 linkuse as main transcript	c.1608_1609insA	3_prime_UTR_variant	18/18
SLC4A1	XM_011525129.3 linkuse as main transcript	c.1608_1609insA	3_prime_UTR_variant	19/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A1	ENST00000262418.12 linkuse as main transcript	c.1608_1609insA		3_prime_UTR_variant	20/20	1	NM_000342.4	P1	P02730-1
SLC4A1	ENST00000399246.3 linkuse as main transcript	c.1608_1609insA		3_prime_UTR_variant	15/15	5

Frequencies

GnomAD3 genomes

AF:

0.0548

AC:

3321

AN:

60616

Hom.:

939

Cov.:

show subpopulations

Gnomad AFR

AF:

0.145

Gnomad AMI

AF:

0.0239

Gnomad AMR

AF:

0.0201

Gnomad ASJ

AF:

0.0297

Gnomad EAS

AF:

0.00947

Gnomad SAS

AF:

0.0160

Gnomad FIN

AF:

0.00538

Gnomad MID

AF:

0.0238

Gnomad NFE

AF:

0.0353

Gnomad OTH

AF:

0.0317

GnomAD4 exome

AF:

0.00118

AC:

AN:

11020

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

AN XY:

5990

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00304

Gnomad4 ASJ exome

AF:

0.0122

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00113

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000973

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0548

AC:

3322

AN:

60622

Hom.:

939

Cov.:

AF XY:

0.0536

AC XY:

1442

AN XY:

26924

show subpopulations

Gnomad4 AFR

AF:

0.145

Gnomad4 AMR

AF:

0.0201

Gnomad4 ASJ

AF:

0.0297

Gnomad4 EAS

AF:

0.00946

Gnomad4 SAS

AF:

0.0161

Gnomad4 FIN

AF:

0.00538

Gnomad4 NFE

AF:

0.0353

Gnomad4 OTH

AF:

0.0329

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Distal Renal Tubular Acidosis, Dominant

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Spherocytosis, Dominant

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Hemolytic anemia

Uncertain:1

Uncertain significance, 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