NM_020428.4:c.461A>G

Variant names:

• chr19-10631494-A-G
• rs2288904
• NM_020428.4:c.461A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020428.4(SLC44A2):​c.461A>G​(p.Gln154Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 1,613,838 control chromosomes in the GnomAD database, including 502,435 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q154P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.83 (52506 hom., cov: 31)
  • Exomes 𝑓: 0.78 (449929 hom.)
• Consequence: SLC44A2 NM_020428.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.829
• Publications: 134 publications found

Genes affected

SLC44A2 (HGNC:17292): (solute carrier family 44 member 2 (CTL2 blood group)) Enables choline transmembrane transporter activity. Involved in choline transport and transmembrane transport. Located in mitochondrion and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.468902E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC44A2	NM_020428.4	c.461A>G	p.Gln154Arg	missense_variant	Exon 7 of 22	ENST00000335757.10	NP_065161.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC44A2	ENST00000335757.10	c.461A>G	p.Gln154Arg	missense_variant	Exon 7 of 22	1	NM_020428.4	ENSP00000336888.4

Frequencies

GnomAD3 genomes AF: 0.828 AC: 125817 AN: 152000 Hom.: 52457 Cov.: 31

Gnomad AFR AF: 0.935

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.813

GnomAD2 exomes AF: 0.801 AC: 201194 AN: 251116 AF XY: 0.793

Gnomad AFR exome AF: 0.939

Gnomad AMR exome AF: 0.881

Gnomad ASJ exome AF: 0.756

Gnomad EAS exome AF: 0.687

Gnomad FIN exome AF: 0.825

Gnomad NFE exome AF: 0.786

Gnomad OTH exome AF: 0.778

GnomAD4 exome AF: 0.783 AC: 1145130 AN: 1461720 Hom.: 449929 Cov.: 77 AF XY: 0.782 AC XY: 568703 AN XY: 727172

African (AFR) AF: 0.938 AC: 31396 AN: 33480

American (AMR) AF: 0.878 AC: 39265 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.757 AC: 19785 AN: 26134

East Asian (EAS) AF: 0.664 AC: 26353 AN: 39696

South Asian (SAS) AF: 0.766 AC: 66102 AN: 86252

European-Finnish (FIN) AF: 0.824 AC: 43932 AN: 53288

Middle Eastern (MID) AF: 0.707 AC: 4079 AN: 5768

European-Non Finnish (NFE) AF: 0.780 AC: 867034 AN: 1111984

Other (OTH) AF: 0.781 AC: 47184 AN: 60394

GnomAD4 genome AF: 0.828 AC: 125924 AN: 152118 Hom.: 52506 Cov.: 31 AF XY: 0.827 AC XY: 61496 AN XY: 74368

African (AFR) AF: 0.935 AC: 38803 AN: 41518

American (AMR) AF: 0.836 AC: 12746 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 2674 AN: 3472

East Asian (EAS) AF: 0.682 AC: 3517 AN: 5156

South Asian (SAS) AF: 0.771 AC: 3721 AN: 4826

European-Finnish (FIN) AF: 0.814 AC: 8629 AN: 10600

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.784 AC: 53281 AN: 67984

Other (OTH) AF: 0.809 AC: 1704 AN: 2106

Alfa AF: 0.791 Hom.: 199882

Bravo AF: 0.832

TwinsUK AF: 0.772 AC: 2862

ALSPAC AF: 0.782 AC: 3012

ESP6500AA AF: 0.934 AC: 4114

ESP6500EA AF: 0.787 AC: 6765

ExAC AF: 0.804 AC: 97608

Asia WGS AF: 0.771 AC: 2682 AN: 3478

EpiCase AF: 0.772

EpiControl AF: 0.772

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	16
DANN	Benign	0.21
DEOGEN2	Benign	0.0021	T;.;T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.036	T;T;T;T;T
MetaRNN	Benign	5.5e-7	T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.5	.;.;N;.;N
PhyloP100		0.83
PrimateAI	Benign	0.47	T
PROVEAN	Benign	0.51	.;N;N;.;.
REVEL	Benign	0.11
Sift	Benign	1.0	.;T;T;.;.
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.0	.;B;B;.;.
Vest4		0.014, 0.013
MPC		0.35
ClinPred		0.0010	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.025
gMVP		0.62
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
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

Other links and lift over

dbSNP: rs2288904; hg19: chr19-10742170; COSMIC: COSV59835474; COSMIC: COSV59835474;