2-168714904-G-T

Variant names:

• chr2-168714904-G-T
• rs13014488
• NM_203463.3:c.610-97G>T

Variant summary

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

The NM_203463.3(CERS6):​c.610-97G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 1,137,022 control chromosomes in the GnomAD database, including 131,462 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 0.37 (12608 hom., cov: 32)
  • Exomes 𝑓: 0.48 (118854 hom.)
• Consequence: CERS6 NM_203463.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.374
• Publications: 2 publications found

Genes affected

CERS6 (HGNC:23826): (ceramide synthase 6) Enables sphingosine N-acyltransferase activity. Involved in ceramide biosynthetic process. Located in 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 (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203463.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERS6	NM_203463.3	MANE Select	c.610-97G>T		intron	N/A	NP_982288.1
	CERS6	NM_001256126.2		c.610-97G>T		intron	N/A	NP_001243055.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERS6	ENST00000305747.11	TSL:2 MANE Select	c.610-97G>T		intron	N/A	ENSP00000306579.6
	CERS6	ENST00000392687.4	TSL:1	c.610-97G>T		intron	N/A	ENSP00000376453.4

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55913 AN: 151878 Hom.: 12611 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.366

GnomAD4 exome AF: 0.480 AC: 473137 AN: 985026 Hom.: 118854 AF XY: 0.482 AC XY: 240638 AN XY: 499302

African (AFR) AF: 0.119 AC: 2628 AN: 22152

American (AMR) AF: 0.287 AC: 8188 AN: 28502

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 7077 AN: 17290

East Asian (EAS) AF: 0.179 AC: 6204 AN: 34600

South Asian (SAS) AF: 0.505 AC: 29838 AN: 59136

European-Finnish (FIN) AF: 0.563 AC: 25127 AN: 44668

Middle Eastern (MID) AF: 0.352 AC: 1243 AN: 3532

European-Non Finnish (NFE) AF: 0.510 AC: 373867 AN: 732384

Other (OTH) AF: 0.444 AC: 18965 AN: 42762

GnomAD4 genome AF: 0.368 AC: 55903 AN: 151996 Hom.: 12608 Cov.: 32 AF XY: 0.372 AC XY: 27648 AN XY: 74260

African (AFR) AF: 0.122 AC: 5073 AN: 41494

American (AMR) AF: 0.302 AC: 4603 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1427 AN: 3468

East Asian (EAS) AF: 0.214 AC: 1107 AN: 5172

South Asian (SAS) AF: 0.496 AC: 2386 AN: 4806

European-Finnish (FIN) AF: 0.573 AC: 6041 AN: 10546

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.501 AC: 34024 AN: 67948

Other (OTH) AF: 0.361 AC: 762 AN: 2112

Alfa AF: 0.376 Hom.: 2509

Bravo AF: 0.332

Asia WGS AF: 0.333 AC: 1158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.041
DANN	Benign	0.52
PhyloP100		-0.37
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: rs13014488; hg19: chr2-169571414;