rs9299385

Variant names:

• chr9-105352222-A-G
• rs9299385
• NM_080546.5:c.500+3771A>G

Variant summary

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

The NM_080546.5(SLC44A1):​c.500+3771A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,258 control chromosomes in the GnomAD database, including 1,956 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 0.10 (1956 hom., cov: 32)
• Consequence: SLC44A1 NM_080546.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.511
• Publications: 0 publications found

Genes affected

SLC44A1 (HGNC:18798): (solute carrier family 44 member 1) Enables choline transmembrane transporter activity. Involved in choline transport and transmembrane transport. Located in several cellular components, including cytosol; mitochondrion; and nucleoplasm. Implicated in high grade glioma. [provided by Alliance of Genome Resources, Apr 2022]

SLC44A1 Gene-Disease associations (from GenCC):

• neurodegeneration, childhood-onset, with ataxia, tremor, optic atrophy, and cognitive decline

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC44A1	NM_080546.5	c.500+3771A>G		intron_variant	Intron 5 of 15	ENST00000374720.8	NP_536856.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC44A1	ENST00000374720.8	c.500+3771A>G		intron_variant	Intron 5 of 15	1	NM_080546.5	ENSP00000363852.3

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15216 AN: 152140 Hom.: 1951 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0478

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00538

Gnomad FIN AF: 0.0146

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0238

Gnomad OTH AF: 0.0735

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.100 AC: 15251 AN: 152258 Hom.: 1956 Cov.: 32 AF XY: 0.0976 AC XY: 7263 AN XY: 74442

African (AFR) AF: 0.301 AC: 12504 AN: 41496

American (AMR) AF: 0.0476 AC: 729 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00497 AC: 24 AN: 4826

European-Finnish (FIN) AF: 0.0146 AC: 155 AN: 10616

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0238 AC: 1620 AN: 68042

Other (OTH) AF: 0.0728 AC: 154 AN: 2116

Alfa AF: 0.0820 Hom.: 196

Bravo AF: 0.113

Asia WGS AF: 0.0230 AC: 79 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.2
DANN	Benign	0.73
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9299385; hg19: chr9-108114503; COSMIC: COSV58262978; COSMIC: COSV58262978;