rs114951054

Variant names:

• chr6-31879123-G-A
• rs114951054
• ENST00000882849.1:c.-143C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000882849.1(SLC44A4):​c.-143C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0419 in 776,524 control chromosomes in the GnomAD database, including 787 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.036 (116 hom., cov: 30)
  • Exomes 𝑓: 0.043 (671 hom.)
• Consequence: SLC44A4 ENST00000882849.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.512
• Publications: 6 publications found

Genes affected

SLC44A4 (HGNC:13941): (solute carrier family 44 member 4) The protein encoded by this gene may be a sodium-dependent transmembrane transport protein involved in the uptake of choline by cholinergic neurons. Defects in this gene can cause sialidosis, a lysosomal storage disease. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

EHMT2-AS1 (HGNC:39751): (EHMT2 and SLC44A4 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-31879123-G-A is Benign according to our data. Variant chr6-31879123-G-A is described in ClinVar as Benign. ClinVar VariationId is 1269640.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.036 (5426/150808) while in subpopulation SAS AF = 0.0536 (250/4660). AF 95% confidence interval is 0.0482. There are 116 homozygotes in GnomAd4. There are 2683 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High AC in GnomAd4 at 5426 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000882849.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHMT2-AS1	NR_174947.1		n.271+1045G>A		intron	N/A
	SLC44A4	NM_025257.3	MANE Select	c.-143C>T		upstream_gene	N/A	NP_079533.2	A0A140VJH4
	SLC44A4	NM_001178044.2		c.-143C>T		upstream_gene	N/A	NP_001171515.1	Q53GD3-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC44A4	ENST00000882849.1		c.-143C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 21	ENSP00000552908.1
	SLC44A4	ENST00000882849.1		c.-143C>T		5_prime_UTR	Exon 1 of 21	ENSP00000552908.1
	EHMT2-AS1	ENST00000642849.1		n.271+1045G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0360 AC: 5418 AN: 150680 Hom.: 115 Cov.: 30

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0285

Gnomad ASJ AF: 0.0240

Gnomad EAS AF: 0.0283

Gnomad SAS AF: 0.0541

Gnomad FIN AF: 0.0565

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0487

Gnomad OTH AF: 0.0333

GnomAD4 exome AF: 0.0433 AC: 27118 AN: 625716 Hom.: 671 AF XY: 0.0440 AC XY: 14204 AN XY: 322786

African (AFR) AF: 0.0154 AC: 247 AN: 16042

American (AMR) AF: 0.0254 AC: 587 AN: 23094

Ashkenazi Jewish (ASJ) AF: 0.0252 AC: 392 AN: 15552

East Asian (EAS) AF: 0.0310 AC: 972 AN: 31306

South Asian (SAS) AF: 0.0491 AC: 2541 AN: 51788

European-Finnish (FIN) AF: 0.0559 AC: 1707 AN: 30512

Middle Eastern (MID) AF: 0.0241 AC: 57 AN: 2364

European-Non Finnish (NFE) AF: 0.0458 AC: 19381 AN: 422946

Other (OTH) AF: 0.0384 AC: 1234 AN: 32112

GnomAD4 genome AF: 0.0360 AC: 5426 AN: 150808 Hom.: 116 Cov.: 30 AF XY: 0.0364 AC XY: 2683 AN XY: 73736

African (AFR) AF: 0.0133 AC: 547 AN: 41248

American (AMR) AF: 0.0289 AC: 439 AN: 15168

Ashkenazi Jewish (ASJ) AF: 0.0240 AC: 83 AN: 3460

East Asian (EAS) AF: 0.0286 AC: 143 AN: 5000

South Asian (SAS) AF: 0.0536 AC: 250 AN: 4660

European-Finnish (FIN) AF: 0.0565 AC: 581 AN: 10288

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0487 AC: 3295 AN: 67690

Other (OTH) AF: 0.0335 AC: 70 AN: 2092

Alfa AF: 0.0370 Hom.: 79

Bravo AF: 0.0314

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.54
PhyloP100		0.51
PromoterAI		-0.023	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs114951054; hg19: chr6-31846900;