19-44708135-T-C

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001039213.4(CEACAM16):c.1215T>C(p.Thr405=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.858 in 1,606,178 control chromosomes in the GnomAD database, including 591,867 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.89 (59993 hom., cov: 33)
  • Exomes 𝑓: 0.85 (531874 hom.)
• Consequence: CEACAM16 NM_001039213.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.92

Genes affected

CEACAM16 (HGNC:31948): (CEA cell adhesion molecule 16, tectorial membrane component) The protein encoded by this gene is a secreted glycoprotein that in mouse interacts with tectorial membrane proteins in the inner ear. The encoded adhesion protein is found in cochlear outer hair cells and appears to be important for proper hearing over an extended frequency range. Defects in this gene likely are a cause of non-syndromic autosomal dominant hearing loss. [provided by RefSeq, May 2012]

CEACAM16-AS1 (HGNC:55317): (CEACAM16, CEACAM19 and PVR antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 19-44708135-T-C is Benign according to our data. Variant chr19-44708135-T-C is described in ClinVar as [Benign]. Clinvar id is 769228.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.92 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEACAM16	NM_001039213.4	c.1215T>C	p.Thr405=	synonymous_variant	6/7	ENST00000587331.7
CEACAM16	XM_017026795.2	c.1215T>C	p.Thr405=	synonymous_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEACAM16	ENST00000587331.7	c.1215T>C	p.Thr405=	synonymous_variant	6/7	1	NM_001039213.4	P1
CEACAM16-AS1	ENST00000662585.1	n.382-8958A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.885 AC: 134654 AN: 152154 Hom.: 59930 Cov.: 33

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.929

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.901

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.854

Gnomad OTH AF: 0.892

GnomAD4 exome AF: 0.855 AC: 1242633 AN: 1453906 Hom.: 531874 Cov.: 73 AF XY: 0.855 AC XY: 617749 AN XY: 722278

Gnomad4 AFR exome AF: 0.973

Gnomad4 AMR exome AF: 0.952

Gnomad4 ASJ exome AF: 0.840

Gnomad4 EAS exome AF: 0.782

Gnomad4 SAS exome AF: 0.894

Gnomad4 FIN exome AF: 0.785

Gnomad4 NFE exome AF: 0.849

Gnomad4 OTH exome AF: 0.865

GnomAD4 genome AF: 0.885 AC: 134775 AN: 152272 Hom.: 59993 Cov.: 33 AF XY: 0.883 AC XY: 65718 AN XY: 74446

Gnomad4 AFR AF: 0.968

Gnomad4 AMR AF: 0.930

Gnomad4 ASJ AF: 0.831

Gnomad4 EAS AF: 0.757

Gnomad4 SAS AF: 0.900

Gnomad4 FIN AF: 0.774

Gnomad4 NFE AF: 0.854

Gnomad4 OTH AF: 0.894

Alfa AF: 0.859 Hom.: 48562

Bravo AF: 0.898

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 30, 2023

The p.Thr405Thr variant in CEACAM16 is classified as benign because it has been identified in 96.8% (40107/41446) of African chromosomes by gnomAD (http://gnomad.broadinstitute.org). Additionally it does not alter an amino acid residue, is not located within the splice consensus site, and computational splice prediction tools do not predict an impact on splicing. ACMG/AMP Criteria applied: BA1, BP4, BP7. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	0.12

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs61744497; hg19: chr19-45211407;