19-17489002-C-A

Variant names:

• chr19-17489002-C-A
• rs115772896
• NM_198580.3:c.887-6C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_198580.3(SLC27A1):​c.887-6C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 1,614,066 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0098 (27 hom., cov: 32)
  • Exomes 𝑓: 0.00094 (22 hom.)
• Consequence: SLC27A1 NM_198580.3 splice_region, intron
• Scores: Splicing: ADA: 0.03585
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.968
• Publications: 2 publications found

Genes affected

SLC27A1 (HGNC:10995): (solute carrier family 27 member 1) Enables biotin transmembrane transporter activity; efflux transmembrane transporter activity; and long-chain fatty acid transporter activity. Involved in several processes, including carboxylic acid transmembrane transport; glycerophospholipid biosynthetic process; and lipid transport across blood-brain barrier. Located in membrane. Part of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

PGLS-DT (HGNC:55274): (PGLS divergent transcript)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 19-17489002-C-A is Benign according to our data. Variant chr19-17489002-C-A is described in ClinVar as Benign. ClinVar VariationId is 781462.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00982 (1494/152212) while in subpopulation AFR AF = 0.0346 (1437/41528). AF 95% confidence interval is 0.0331. There are 27 homozygotes in GnomAd4. There are 691 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 27 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198580.3. 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
	SLC27A1	NM_198580.3	MANE Select	c.887-6C>A		splice_region intron	N/A	NP_940982.1	Q6PCB7-1
	PGLS-DT	NR_147835.1		n.763G>T		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC27A1	ENST00000252595.12	TSL:1 MANE Select	c.887-6C>A		splice_region intron	N/A	ENSP00000252595.6	Q6PCB7-1
	SLC27A1	ENST00000865647.1		c.887-6C>A		splice_region intron	N/A	ENSP00000535706.1
	SLC27A1	ENST00000865653.1		c.887-6C>A		splice_region intron	N/A	ENSP00000535712.1

Frequencies

GnomAD3 genomes AF: 0.00980 AC: 1491 AN: 152094 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.0346

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00527

GnomAD2 exomes AF: 0.00242 AC: 608 AN: 251368 AF XY: 0.00163

Gnomad AFR exome AF: 0.0340

Gnomad AMR exome AF: 0.00136

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000937 AC: 1370 AN: 1461854 Hom.: 22 Cov.: 32 AF XY: 0.000770 AC XY: 560 AN XY: 727244

African (AFR) AF: 0.0349 AC: 1169 AN: 33480

American (AMR) AF: 0.00132 AC: 59 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.0000225 AC: 25 AN: 1111980

Other (OTH) AF: 0.00182 AC: 110 AN: 60392

GnomAD4 genome AF: 0.00982 AC: 1494 AN: 152212 Hom.: 27 Cov.: 32 AF XY: 0.00929 AC XY: 691 AN XY: 74418

African (AFR) AF: 0.0346 AC: 1437 AN: 41528

American (AMR) AF: 0.00268 AC: 41 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 67998

Other (OTH) AF: 0.00521 AC: 11 AN: 2110

Alfa AF: 0.00520 Hom.: 4

Bravo AF: 0.0107

Asia WGS AF: 0.000577 AC: 2 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	-0.39
CADD	Benign	15
DANN	Benign	0.94
PhyloP100		0.97
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.036
dbscSNV1_RF	Benign	0.29
SpliceAI score (max)		0.10		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: rs115772896; hg19: chr19-17599811;