5-128538228-C-G

Variant names:

• chr5-128538228-C-G
• rs147684576
• NM_001999.4:c.-625G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001999.4(FBN2):​c.-625G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0798 in 153,932 control chromosomes in the GnomAD database, including 615 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.080 (609 hom., cov: 30)
  • Exomes 𝑓: 0.059 (6 hom.)
• Consequence: FBN2 NM_001999.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.01
• Publications: 2 publications found

Genes affected

FBN2 (HGNC:3604): (fibrillin 2) The protein encoded by this gene is a component of connective tissue microfibrils and may be involved in elastic fiber assembly. Mutations in this gene cause congenital contractural arachnodactyly. [provided by RefSeq, Jul 2008]

SLC27A6 (HGNC:11000): (solute carrier family 27 member 6) This gene encodes a member of the fatty acid transport protein family (FATP). FATPs are involved in the uptake of long-chain fatty acids and have unique expression patterns. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 5-128538228-C-G is Benign according to our data. Variant chr5-128538228-C-G is described in ClinVar as Benign. ClinVar VariationId is 683525.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001999.4. 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
	FBN2	NM_001999.4	MANE Select	c.-625G>C		5_prime_UTR	Exon 1 of 65	NP_001990.2	P35556-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBN2	ENST00000262464.9	TSL:1 MANE Select	c.-625G>C		5_prime_UTR	Exon 1 of 65	ENSP00000262464.4	P35556-1
	FBN2	ENST00000939405.1		c.-625G>C		5_prime_UTR	Exon 1 of 64	ENSP00000609464.1
	FBN2	ENST00000939404.1		c.-625G>C		5_prime_UTR	Exon 1 of 64	ENSP00000609463.1

Frequencies

GnomAD3 genomes AF: 0.0803 AC: 12110 AN: 150868 Hom.: 610 Cov.: 30

Gnomad AFR AF: 0.0235

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0688

Gnomad ASJ AF: 0.0884

Gnomad EAS AF: 0.0665

Gnomad SAS AF: 0.0799

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0705

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.0768

GnomAD4 exome AF: 0.0586 AC: 173 AN: 2954 Hom.: 6 Cov.: 0 AF XY: 0.0577 AC XY: 104 AN XY: 1802

African (AFR) AF: 0.00 AC: 0 AN: 48

American (AMR) AF: 0.0333 AC: 1 AN: 30

Ashkenazi Jewish (ASJ) AF: 0.0179 AC: 1 AN: 56

East Asian (EAS) AF: 0.0145 AC: 2 AN: 138

South Asian (SAS) AF: 0.0703 AC: 62 AN: 882

European-Finnish (FIN) AF: 0.0342 AC: 5 AN: 146

Middle Eastern (MID) AF: 0.0833 AC: 1 AN: 12

European-Non Finnish (NFE) AF: 0.0606 AC: 92 AN: 1518

Other (OTH) AF: 0.0726 AC: 9 AN: 124

GnomAD4 genome AF: 0.0802 AC: 12105 AN: 150978 Hom.: 609 Cov.: 30 AF XY: 0.0796 AC XY: 5870 AN XY: 73702

African (AFR) AF: 0.0234 AC: 965 AN: 41184

American (AMR) AF: 0.0688 AC: 1046 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.0884 AC: 306 AN: 3460

East Asian (EAS) AF: 0.0661 AC: 331 AN: 5004

South Asian (SAS) AF: 0.0795 AC: 378 AN: 4752

European-Finnish (FIN) AF: 0.107 AC: 1112 AN: 10406

Middle Eastern (MID) AF: 0.0724 AC: 21 AN: 290

European-Non Finnish (NFE) AF: 0.114 AC: 7692 AN: 67674

Other (OTH) AF: 0.0760 AC: 160 AN: 2104

Alfa AF: 0.0919 Hom.: 106

Bravo AF: 0.0754

Asia WGS AF: 0.0870 AC: 302 AN: 3470

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	-0.76
CADD	Benign	16
DANN	Benign	0.57
PhyloP100		1.0
PromoterAI		-0.020	Neutral
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: rs147684576; hg19: chr5-127873921;