rs7821494

Variant names:

• chr8-143729461-C-G
• rs7821494
• NM_198488.5:c.448-138G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-143729461-C-G
• chr8-143729461-C-T

Variant summary

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

The NM_198488.5(FAM83H):​c.448-138G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 938,528 control chromosomes in the GnomAD database, including 27,318 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (4895 hom., cov: 32)
  • Exomes 𝑓: 0.23 (22423 hom.)
• Consequence: FAM83H NM_198488.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.372
• Publications: 4 publications found

Genes affected

FAM83H (HGNC:24797): (family with sequence similarity 83 member H) The protein encoded by this gene plays an important role in the structural development and calcification of tooth enamel. Defects in this gene are a cause of amelogenesis imperfecta type 3 (AI3). [provided by RefSeq, Mar 2010]

FAM83H Gene-Disease associations (from GenCC):

• amelogenesis imperfecta, type 3A

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 8-143729461-C-G is Benign according to our data. Variant chr8-143729461-C-G is described in ClinVar as Benign. ClinVar VariationId is 1279352.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198488.5. 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
	FAM83H	NM_198488.5	MANE Select	c.448-138G>C		intron	N/A	NP_940890.4	Q6ZRV2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM83H	ENST00000388913.4	TSL:5 MANE Select	c.448-138G>C		intron	N/A	ENSP00000373565.3	Q6ZRV2
	FAM83H	ENST00000650760.1		c.1051-138G>C		intron	N/A	ENSP00000499217.1	A0A494C1T9
	FAM83H	ENST00000935286.1		c.448-138G>C		intron	N/A	ENSP00000605345.1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37226 AN: 151900 Hom.: 4883 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.0813

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.243

GnomAD4 exome AF: 0.225 AC: 177087 AN: 786510 Hom.: 22423 AF XY: 0.226 AC XY: 92072 AN XY: 406510

African (AFR) AF: 0.276 AC: 5506 AN: 19936

American (AMR) AF: 0.299 AC: 10067 AN: 33638

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 4404 AN: 19970

East Asian (EAS) AF: 0.495 AC: 16293 AN: 32914

South Asian (SAS) AF: 0.253 AC: 16420 AN: 64880

European-Finnish (FIN) AF: 0.254 AC: 9321 AN: 36730

Middle Eastern (MID) AF: 0.277 AC: 817 AN: 2946

European-Non Finnish (NFE) AF: 0.196 AC: 105228 AN: 537726

Other (OTH) AF: 0.239 AC: 9031 AN: 37770

GnomAD4 genome AF: 0.245 AC: 37275 AN: 152018 Hom.: 4895 Cov.: 32 AF XY: 0.250 AC XY: 18559 AN XY: 74292

African (AFR) AF: 0.275 AC: 11394 AN: 41440

American (AMR) AF: 0.251 AC: 3843 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 785 AN: 3468

East Asian (EAS) AF: 0.517 AC: 2657 AN: 5144

South Asian (SAS) AF: 0.270 AC: 1302 AN: 4818

European-Finnish (FIN) AF: 0.256 AC: 2702 AN: 10572

Middle Eastern (MID) AF: 0.312 AC: 91 AN: 292

European-Non Finnish (NFE) AF: 0.204 AC: 13901 AN: 67976

Other (OTH) AF: 0.249 AC: 526 AN: 2110

Alfa AF: 0.124 Hom.: 214

Bravo AF: 0.249

Asia WGS AF: 0.399 AC: 1385 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	-0.90
CADD	Benign	3.4
DANN	Benign	0.62
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: rs7821494; hg19: chr8-144811631;