7-30912043-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_198098.4(AQP1):c.134C>T(p.Ala45Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0363 in 1,613,408 control chromosomes in the GnomAD database, including 1,258 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.027 (83 hom., cov: 32)
  • Exomes 𝑓: 0.037 (1175 hom.)
• Consequence: AQP1 NM_198098.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.654

Genes affected

AQP1 (HGNC:633): (aquaporin 1 (Colton blood group)) This gene encodes a small integral membrane protein with six bilayer spanning domains that functions as a water channel protein. This protein permits passive transport of water along an osmotic gradient. This gene is a possible candidate for disorders involving imbalance in ocular fluid movement. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002882719).
• BP6: Variant 7-30912043-C-T is Benign according to our data. Variant chr7-30912043-C-T is described in ClinVar as [Benign]. Clinvar id is 17846.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-30912043-C-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0269 (4100/152294) while in subpopulation NFE AF= 0.0419 (2848/68018). AF 95% confidence interval is 0.0406. There are 83 homozygotes in gnomad4. There are 1940 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 83 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AQP1	NM_198098.4	c.134C>T	p.Ala45Val	missense_variant	1/4	ENST00000311813.11
AQP1	NM_001329872.2	c.134C>T	p.Ala45Val	missense_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AQP1	ENST00000311813.11	c.134C>T	p.Ala45Val	missense_variant	1/4	1	NM_198098.4	P1
AQP1	ENST00000652696.1	c.134C>T	p.Ala45Val	missense_variant	1/5			P1
AQP1	ENST00000441328.7			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.0270 AC: 4103 AN: 152176 Hom.: 83 Cov.: 32

Gnomad AFR AF: 0.0101

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0144

Gnomad ASJ AF: 0.0109

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.0423

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0419

Gnomad OTH AF: 0.0205

GnomAD3 exomes AF: 0.0260 AC: 6529 AN: 251044 Hom.: 122 AF XY: 0.0265 AC XY: 3598 AN XY: 135840

Gnomad AFR exome AF: 0.00808

Gnomad AMR exome AF: 0.0111

Gnomad ASJ exome AF: 0.00923

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00591

Gnomad FIN exome AF: 0.0380

Gnomad NFE exome AF: 0.0420

Gnomad OTH exome AF: 0.0251

GnomAD4 exome AF: 0.0372 AC: 54398 AN: 1461114 Hom.: 1175 Cov.: 33 AF XY: 0.0363 AC XY: 26418 AN XY: 726874

Gnomad4 AFR exome AF: 0.00774

Gnomad4 AMR exome AF: 0.0110

Gnomad4 ASJ exome AF: 0.00999

Gnomad4 EAS exome AF: 0.00141

Gnomad4 SAS exome AF: 0.00537

Gnomad4 FIN exome AF: 0.0386

Gnomad4 NFE exome AF: 0.0440

Gnomad4 OTH exome AF: 0.0310

GnomAD4 genome AF: 0.0269 AC: 4100 AN: 152294 Hom.: 83 Cov.: 32 AF XY: 0.0261 AC XY: 1940 AN XY: 74472

Gnomad4 AFR AF: 0.0101

Gnomad4 AMR AF: 0.0144

Gnomad4 ASJ AF: 0.0109

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.00456

Gnomad4 FIN AF: 0.0423

Gnomad4 NFE AF: 0.0419

Gnomad4 OTH AF: 0.0203

Alfa AF: 0.0340 Hom.: 156

Bravo AF: 0.0239

TwinsUK AF: 0.0475 AC: 176

ALSPAC AF: 0.0392 AC: 151

ESP6500AA AF: 0.0127 AC: 56

ESP6500EA AF: 0.0409 AC: 352

ExAC AF: 0.0263 AC: 3198

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.0391

EpiControl AF: 0.0366

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

COLTON BLOOD GROUP POLYMORPHISM Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Sep 01, 1994

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 07, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.47
Cadd	Benign	13
Dann	Uncertain	0.98
DEOGEN2	Uncertain	0.48	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.86	L
MutationTaster	Benign	1.0	N;N
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.17
Sift	Benign	0.15	T
Sift4G	Benign	0.44	T
Polyphen		0.0070	B
Vest4		0.059
MPC		0.41
ClinPred		0.0044	T
GERP RS		0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs28362692; hg19: chr7-30951658;